Rhinovirus

From Wikipedia, the free encyclopedia "Human rhinovirus"

Molecular surface of a Human rhinovirus, showing protein spikes

Virus classification Group: Group IV ((+)ssRNA) Order: Picornavirales Family: Picornaviridae Genus: Enterovirus Type species Human enterovirus C Species Human rhinovirus A Human rhinovirus B Human rhinovirus C Human rhinoviruses (from the Greek , (gen.) "nose") are the most common viral infective agents in humans and are the predominant cause of the common cold. Rhinovirus infection proliferates in temperatures between 3335 C (9195 F), and this may be why it occurs primarily in the nose. Rhinovirus is a species in the genus Enterovirus of the Picornaviridae family of viruses. There are 99 recognized types of Human rhinoviruses that differ according to their surface proteins. They are lytic in nature and are among the smallest viruses, with diameters of about only 30 nanometers. Other viruses such as smallpox and vaccinia are around 10 times larger at about 300 nanometers.

Contents
[hide]

1 Transmission and epidemiology

2 Pathogenesis 3 Taxonomy 4 Structure 5 Novel antiviral drugs 6 Vaccine 7 References 8 External links

[edit] Transmission and epidemiology

Main article: Common cold There are two modes of transmission: via aerosols of respiratory droplets and from contaminated surfaces, including direct person-to-person contact. Human rhinoviruses occur worldwide and are the primary cause of common colds. Symptoms include sore throat, runny nose, nasal congestion, sneezing and cough; sometimes accompanied by muscle aches, fatigue, malaise, headache, muscle weakness, or loss of appetite. Fever and extreme exhaustion are more usual in influenza. Children may have six to twelve colds a year. In the United States, the incidence of colds is higher in the autumn and winter, with most infections occurring between September to April. The seasonality may be due to the start of the school year, or due to people spending more time indoors (thus in closer proximity with each other), increasing the chance of transmission of the virus.

[edit] Pathogenesis
The primary route of entry for Human rhinoviruses is the upper respiratory tract. Afterward, the virus binds to ICAM-1 (Inter-Cellular Adhesion Molecule 1) also known as CD54 (Cluster of Differentiation 54) receptors on respiratory epithelial cells. As the virus replicates and spreads, infected cells release distress signals known as chemokines and cytokines (which in turn activate inflammatory mediators). Infection occurs rapidly, with the virus adhering to surface receptors within 15 minutes of entering the respiratory tract. Just over 50% of symptomatic individuals will experience symptoms within 2 days of infection. Only about 5% of cases will have an incubation period of less than 20 hours, and, on the other end, it is expected that 5% of cases would have an incubation period of greater than four and a half days.[1] Human rhinoviruses preferentially grow at 32C (89F) as opposed to 37C (98F), hence infect the upper respiratory tract.

[edit] Taxonomy

Rhinovirus was formerly a genus from the family Picornaviridae. The 39th Executive Committee (EC39) of the International Committee on Taxonomy of Viruses (ICTV) met in Canada during June 2007 with new taxonomic proposals. In April 2008, the International Committee on Taxonomy of Viruses voted and ratified the following changes:

2005.264V.04 To remove the following species from the existing genus Rhinovirus in the family Picornaviridae: o Human rhinovirus A o Human rhinovirus B 2005.265V.04 To assign the following species to the genus Enterovirus in the family Picornaviridae: o Human rhinovirus A o Human rhinovirus B 2005.266V.04 To remove the existing genus Rhinovirus from the family Picornaviridae. Note: The genus Rhinovirus hereby disappears.

In July 2009, the ICTV voted and ratified a proposal to add a third species, Human rhinovirus C to the genus Enterovirus.

2008.084V.A.HRV-C-Sp 2008.084V To create a new species named Human rhinovirus C in the genus Enterovirus, family Picornaviridae.

There have been a total of 215 taxonomic proposals, which have been approved and ratified since the 8th ICTV Report of 2005. Rhinovirus C, unlike the A and B species, may be able to cause severe infections.[2]

[edit] Structure
Rhinoviruses have single-stranded positive sense RNA genomes of between 7.2 and 8.5 kb in length. At the 5' end of the genome is a virus-encoded protein, and like mammalian mRNA, there is a 3' poly-A tail. Structural proteins are encoded in the 5' region of the genome and non structural at the 3' end. This is the same for all picornaviruses. The viral particles themselves are not enveloped and are icosahedral in structure. The viral proteins are transcribed as a single, long polypeptide, which is cleaved into the structural and nonstructural viral proteins.[3] Human rhinoviruses are composed of a capsid, that contains four viral proteins VP1, VP2, VP3 and VP4.[4][5] VP1, VP2, and VP3 form the major part of the protein capsid. The much smaller VP4 protein has a more extended structure, and lies at interface between the capsid and the RNA genome. There are 60 copies of each of these proteins assembled as an icosahedron. Antibodies are a major defense against infection with the epitopes lying on the exterior regions of VP1-VP3.

[edit] Novel antiviral drugs

Interferon-alpha used intranasally was shown to be effective against Human rhinovirus infections. However, volunteers treated with this drug experienced some side effects, such as nasal bleeding, and began developing resistance to the drug. Subsequently, research into the treatment was abandoned. Pleconaril is an orally bioavailable antiviral drug being developed for the treatment of infections caused by picornaviruses.[6] This drug acts by binding to a hydrophobic pocket in VP1, and stabilizes the protein capsid to such an extent that the virus cannot release its RNA genome into the target cell. When tested in volunteers, during the clinical trials, this drug caused a significant decrease in mucus secretions and illness-associated symptoms. Pleconaril is not currently available for treatment of Human rhinoviral infections, as its efficacy in treating these infections is under further evaluation.[7] There are potentially other substances such as Iota-Carrageenan that may lead to the creation of drugs to combat the Human rhinovirus.[8] In Asthma: Human rhinoviruses have been recently associated with the majority of asthma exacerbations for which current therapy is inadequate. Intercellular adhesion molecule 1 (ICAM1) has a central role in airway inflammation in asthma, and it is the receptor for 90% of Human rhinoviruses. Human rhinovirus infection of airway epithelium induces ICAM-1. Desloratadine and loratadine are compounds belonging to the new class of H1-receptor blockers. Antiinflammatory properties of antihistamines have been recently documented, although the underlying molecular mechanisms are not completely defined. These effects are unlikely to be mediated by H1-receptor antagonism and suggest a novel mechanism of action that may be important for the therapeutic control of virus-induced asthma exacerbations.

[edit] Vaccine
There are no vaccines against these viruses as there is little-to-no cross-protection between serotypes. At least 99 serotypes of Human rhinoviruses affecting humans have been sequenced.[9] [10] However, recent study of the VP4 protein has shown it to be highly conserved amongst many serotypes of Human rhinovirus,[11] opening up the potential for a future pan-serotype Human rhinovirus vaccine.

Coronavirus
From Wikipedia, the free encyclopedia Coronavirus

Virus classification Group: Group IV ((+)ssRNA) Order: Nidovirales Family: Coronaviridae Subfamily: Coronavirinae Genus Alphacoronavirus Betacoronavirus Gammacoronavirus Coronaviruses are species in the genera of virus belonging to the subfamily Coronavirinae in the family Coronaviridae.[1] Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome and a helical symmetry. The genomic size of coronaviruses ranges from approximately 16 to 31 kilobases, extraordinarily large for an RNA virus. The name "coronavirus" is derived from the Greek , meaning crown, as the virus envelope appears under electron microscopy (E.M.) to be crowned by a characteristic ring of small bulbous structures. This morphology is actually formed by the viral spike (S) peplomers, which are proteins that populate the surface of the virus and determine host tropism. Coronaviruses are grouped in the order Nidovirales, named for the Latin nidus, meaning nest, as all viruses in this order produce a 3' co-terminal nested set of subgenomic mRNA's during infection. Proteins that contribute to the overall structure of all coronaviruses are the spike (S), envelope (E), membrane (M) and nucleocapsid (N). In the specific case of SARS (see below), a defined receptor-binding domain on S mediates the attachment of the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2).[2] Members of the group 2 coronaviruses also have a shorter spike-like protein called hemagglutinin esterase (HE) encoded in their genome, but for some reason this protein is not always brought to expression (produced) in the cell.[3]

Contents
[hide]

1 Diseases of coronavirus 2 Replication 3 Severe acute respiratory syndrome

4 Recent discoveries of novel human coronaviruses 5 Species 6 References 7 External links

[edit] Diseases of coronavirus

Coronaviruses primarily infect the upper respiratory and gastrointestinal tract of mammals and birds. Four to five different currently known strains of coronaviruses infect humans. The most publicized human coronavirus, SARS-CoV which causes SARS, has a unique pathogenesis because it causes both upper and lower respiratory tract infections and can also cause gastroenteritis. Coronaviruses are believed to cause a significant percentage of all common colds in human adults. Coronaviruses cause colds in humans primarily in the winter and early spring seasons. The significance and economic impact of coronaviruses as causative agents of the common cold are hard to assess because, unlike rhinoviruses (another common cold virus), human coronaviruses are difficult to grow in the laboratory. Coronaviruses also cause a range of diseases in farm animals and domesticated pets, some of which can be serious and are a threat to the farming industry. Economically significant coronaviruses of farm animals include porcine coronavirus (transmissible gastroenteritis coronavirus, TGE) and bovine coronavirus, which both result in diarrhea in young animals. Feline Coronavirus: 2 forms, Feline enteric coronavirus is a pathogen of minor clinical significance, but spontaneous mutation of this virus can result in feline infectious peritonitis (FIP), a disease associated with high mortality. There are two types of canine coronavirus (CCoV), one that causes mild gastrointestinal disease and one that has been found to cause respiratory disease. Mouse hepatitis virus (MHV) is a coronavirus that causes an epidemic murine illness with high mortality, especially among colonies of laboratory mice. Prior to the discovery of SARS-CoV, MHV had been the best-studied coronavirus both in vivo and in vitro as well as at the molecular level. Some strains of MHV cause a progressive demyelinating encephalitis in mice which has been used as a murine model for multiple sclerosis. Significant research efforts have been focused on elucidating the viral pathogenesis of these animal coronaviruses, especially by virologists interested in veterinary and zoonotic diseases.

[edit] Replication

The infection cycle of coronavirus Replication of Coronavirus begins with entry to the cell takes place in the cytoplasm in a membrane-protected microenvironment, upon entry to the cell the virus particle is uncoated and the RNA genome is deposited into the cytoplasm. The Coronavirus genome has a 5 methylated cap and a 3polyadenylated-A tail to make it look as much like the host RNA as possible. This also allows the RNA to attach to ribosomes for translation. Coronaviruses also have a protein known as a replicase encoded in its genome which allows the RNA viral genome to be transcribed into new RNA copies using the host cells machinery. The replicase is the first protein to be made as once the gene encoding the replicase is translated the translation is stopped by a stop codon. This is known as a nested transcript, where the transcript only encodes one gene- it is monocistronic. The RNA genome is replicated and a long polyprotein is formed, where all of the proteins are attached. Coronaviruses have a non-structural protein called a protease which is able to separate the proteins in the chain. This is a form of genetic economy for the virus allowing it to encode the most amounts of genes in a small amount of nucleotides. Coronavirus transcription involves a discontinuous RNA synthesis (template switch) during the extension of a negative copy of the subgenomic mRNAs. Basepairing during transcription is a requirement. Coronavirus N protein is required for coronavirus RNA synthesis, and has RNA chaperone activity that may be involved in template switch. Both viral and cellular proteins are required for replication and transcription. Coronaviruses initiate translation by cap-dependent and cap-independent mechanisms. Cell macromolecular synthesis may be controlled after Coronavirus infection by locating some virus proteins in the host cell nucleus. Infection by different coronaviruses cause in the host alteration in the transcription and translation patterns, in the cell cycle, the cytoskeleton, apoptosis and coagulation pathways, inflammation, and immune and stress responses.[4]

[edit] Severe acute respiratory syndrome

Main article: Severe acute respiratory syndrome

In 2003, following the outbreak of Severe acute respiratory syndrome (SARS) which had begun the prior year in Asia, and secondary cases elsewhere in the world, the World Health Organization issued a press release stating that a novel coronavirus identified by a number of laboratories was the causative agent for SARS. The virus was officially named the SARS coronavirus (SARS-CoV). The SARS epidemic resulted in over 8000 infections, about 10% of which resulted in death.[2] Xray crystallography studies performed at the Advanced Light Source of Lawrence Berkeley National Laboratory have begun to give hope of a vaccine against the disease "since [the spike protein] appears to be recognized by the immune system of the host."[5]

[edit] Recent discoveries of novel human coronaviruses

Following the high-profile publicity of SARS outbreaks, there has been a renewed interest in coronaviruses in the field of virology. For many years, scientists knew only about the existence of two human coronaviruses (HCoV-229E and HCoV-OC43). The discovery of SARS-CoV added another human coronavirus to the list. By the end of 2004, three independent research labs reported the discovery of a fourth human coronavirus. It has been named NL63, NL or the New Haven coronavirus by the different research groups.[6] The naming of this fourth coronavirus is still a controversial issue, because the three labs are still battling over who actually discovered the virus first and hence earns the right to name the virus. Early in 2005, a research team at the University of Hong Kong reported finding a fifth human coronavirus in two pneumonia patients, and subsequently named it HKU1.

[edit] Species

Genus: Alphacoronavirus; type species: Alphacoronavirus 1 o Species: Alphacoronavirus 1, Human coronavirus 229E, Human coronavirus NL63, Miniopterus Bat coronavirus 1, Miniopterus Bat coronavirus HKU8, Porcine epidemic diarrhea virus, Rhinolophus Bat coronavirus HKU2, Scotophilus Bat coronavirus 512 Genus Betacoronavirus; type species: Murine coronavirus o Species: Betacoronavirus 1, Human coronavirus HKU1, Murine coronavirus, Pipistrellus Bat coronavirus HKU5, Rousettus Bat coronavirus HKU9, Severe acute respiratory syndrome-related coronavirus, Tylonycteris Bat coronavirus HKU4 Genus Gammacoronavirus; type species: Avian coronavirus o Species: Avian coronavirus, Beluga whale coronavirus SW1

In April 2008, the following proposals were ratified by the ICTV:[7]

2005.260V.04 To create the following species in the genus Coronavirus in the family Coronaviridae, named Goose coronavirus, Pigeon coronavirus, Duck coronavirus. 2006.009V.04 To create a species in the genus Coronavirus in the family Coronaviridae, named Human coronavirus NL63.

2006.010V.04 To create a species in the genus Coronavirus in the family Coronaviridae, named Human coronavirus HKU1. 2006.011V.04 To create a species in the genus Coronavirus in the family Coronaviridae, named Equine coronavirus.

In July 2009, the following proposals were ratified by the ICTV:[8]

2008.085-122V.A.v3.Coronaviridae 2008.085V Create a new subfamily in the family Coronaviridae, order Nidovirales 2008.086V Name the new subfamily Coronavirinae 2008.087V Create a new genus in the proposed subfamily Coronavirinae 2008.088V Name the new genus Alphacoronavirus 2008.089V Assign three existing species (Human coronavirus 229E, Human coronavirus NL63, Porcine epidemic diarrhea virus) and five new species proposed in 2008.091095V.01 to the proposed new genus Alphacoronavirus 2008.090V Designate proposed species Alphacoronavirus 1 as type species of the genus Alphacoronavirus 2008.091V Create new species named Alphacoronavirus 1 in the new genus 2008.092V Create new species named Rhinolophus bat coronavirus HKU2 in the new genus 2008.093V Create new species named Scotophilus bat coronavirus 512 in the new genus 2008.094V Create new species named Miniopterus bat coronavirus 1 in the new genus 2008.095V Create new species named Miniopterus bat coronavirus HKU8 in the new genus 2008.096V Create a new genus in the proposed subfamily Coronavirinae 2008.097V Name the new genus Betacoronavirus 2008.098V Assign the existing species Human coronavirus HKU1 and six new species proposed in 2008.100-105V.01 to the proposed genus Betacoronavirus 2008.099V Designate proposed species Murine coronavirus as type species of the genus Betacoronavirus 2008.108V Assign the two species proposed in 2008.110,111V.01 to the new genus 2008.109V Designate proposed species Avian coronavirus as type species of the new genus 2008.110V Create species named Avian coronavirus in the new genus 2008.111V Create species named Beluga whale coronavirus SW1 in the new genus 2008.112V Create a new subfamily in the family Coronaviridae, order Nidovirales 2008.113V Name the new subfamily Torovirinae 2008.114V Create a new genus in the subfamily Torovirinae 2008.115V Name the new genus Bafinivirus 2008.116V Assign the species White breamVirus (proposed in 2008.118V.01) to the new genus 2008.117V Designate species White bream virus as type species in the new genus 2008.118V Create species named White bream virus in the new genus 2008.119V Remove the genus Torovirus from the family Coronaviridae 2008.120V Reassign the genus Torovirus to the subfamily Torovirinae

2008.121V.U Remove (abolish) 18 species (Human enteric coronavirus, Human coronavirus OC43, Bovine coronavirus, Porcine hemagglutinating encephalomyelitis virus, Equine coronavirus, Murine hepatitis virus, Puffinosis coronavirus, Rat coronavirus, Transmissible gastroenteritis virus, Canine coronavirus, Feline coronavirus, Infectious bronchitis virus, Duck coronavirus, Goose coronavirus, Pheasant coronavirus, Pigeon coronavirus, Turkey coronavirus, Severe acute respiratory syndrome coronavirus) from the genus Coronavirus 2008.122V.U Reassign species Human coronavirus 229E, Human coronavirus NL63 and Porcine epidemic diarrhea virus to the new genus Alphacoronavirus and Human coronavirus HKU1 to the new genus Betacoronavirus

Orthomyxoviridae
From Wikipedia, the free encyclopedia (Redirected from Influenza virus) Orthomyxoviridae Virus classification Group: Group V ((-)ssRNA) Order: Unassigned Family: Orthomyxoviridae Genera

Influenzavirus A Influenzavirus B Influenzavirus C Isavirus Thogotovirus

Influenza (Flu)

Types

Avian (A/H5N1 subtype) Canine Equine Swine (A/H1N1 subtype)

Vaccines

2009 pandemic (Pandemrix) ACAM-FLU-A Fluzone Influvac Live attenuated (FluMist) Optaflu

Treatment

Amantadine Arbidol Laninamivir Oseltamivir Peramivir Rimantadine Vitamin D Zanamivir

Pandemics

2009 Swine 19681969 Hong Kong 1918

Outbreaks

2008 West Bengal 2007 Bernard Matthews H5N1

2007 Australian equine 2006 H5N1 India 1976 swine flu

See also

Flu season Influenza evolution Influenza research Influenza-like illness

vde

The Orthomyxoviridae (orthos, Greek for "straight"; myxa, Greek for "mucus")[1] are a family of RNA viruses that includes five genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Isavirus and Thogotovirus. A sixth has recently been described.[2] The first three genera contain viruses that cause influenza in vertebrates, including birds (see also avian influenza), humans, and other mammals. Isaviruses infect salmon; thogotoviruses infect vertebrates and invertebrates, such as mosquitoes and sea lice.[3][4][5] The three genera of Influenzavirus, which are identified by antigenic differences in their nucleoprotein and matrix protein infect vertebrates as follows:

Influenzavirus A infects humans, other mammals, and birds, and causes all flu pandemics Influenzavirus B infects humans and seals Influenzavirus C infects humans and pigs

Contents
[hide]

1 Classification 2 Types o 2.1 Influenza A o 2.2 Influenza B o 2.3 Influenza C 3 Virology o 3.1 Morphology o 3.2 Genome o 3.3 Structure

3.4 Life cycle 4 Viability and disinfection 5 Vaccination and Prophylaxis 6 References
o

7 External links

[edit] Classification
In a phylogenetic-based taxonomy the "RNA viruses" includes the "negative-sense ssRNA viruses" which includes the Order "Mononegavirales", and the Family "Orthomyxoviridae" (among others). The genera-associated species and serotypes of Orthomyxoviridae are shown in the following table.
Orthomyxoviridae Genera, Species, and Serotypes Genus Species (* indicates type species) Serotypes or Subtypes H1N1, H3N1, H5N1, H5N8, H7N2, H7N7, H1N2, H3N2, H5N2, H5N9, H7N3, H9N2, H2N2, H3N8, H5N3, H7N1, H7N4, H10N7 Hosts

Influenzavirus A Influenza A virus*

Human, pig, bird, horse

Influenzavirus B Influenza B virus* Influenzavirus C Influenza C virus* Isavirus Infectious salmon anemia virus* Thogoto virus* Thogotovirus Dhori virus

Human, seal Human, pig Atlantic salmon Tick, mosquito, mammal Batken virus, Dhori virus (including human)

Quaranfil virus, Johnston Atoll virus, Lake Chad virus

[edit] Types

There are four genera of influenza virus: Influenzavirus A, Influenzavirus B, Influenzavirus C and Ryanovirus. Each genus includes only one species, or type: Influenza A virus, Influenza B virus, and Influenza C virus, respectively. Influenza A and C infect multiple species, while influenza B almost exclusively infects humans.[6][7]
[edit] Influenza A Main article: Influenzavirus A

Influenza A viruses are further classified, based on the viral surface proteins hemagglutinin (HA or H) and neuraminidase (NA or N)... Sixteen H subtypes (or serotypes) and nine N subtypes of influenza A virus have been identified.

Diagram of influenza nomenclature.

Further variation exists; thus, specific influenza strain isolates are identified by a standard nomenclature specifying virus type, geographical location where first isolated, sequential number of isolation, year of isolation, and HA and NA subtype.[8][9] Examples of the nomenclature are:
1. A/Brisbane/59/2007 (H1N1) 2. A/Moscow/10/99 (H3N2)

The type A viruses are the most virulent human pathogens among the three influenza types and causes the most severe disease. The serotypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:

H1N1 caused "Spanish Flu" in 1918, "Swine flu" in 2009.[10] H2N2 caused "Asian Flu". H3N2 caused "Hong Kong Flu". H5N1 is a pandemic threat. H7N7 has unusual zoonotic potential.[11] H1N2 is endemic in humans and pigs. H9N2, H7N2, H7N3, H10N7.

Flu pandemics[12] Name Year Deaths (millions) Subtype involved possibly H2N2 H1N1 H2N2 H3N2 H1N1

Asiatic 18891 (Russian) Flu 90 Spanish Flu Asian Flu Hong Kong Flu Swine Flu 191840 20 19571-1.5 58 19680.75 69 2009 - ...

[edit] Influenza B Main article: Influenzavirus B

Influenza B virus is almost exclusively a human pathogen, and is less common than influenza A. The only other animal known to be susceptible to influenza B infection is the seal.[13] This type of influenza mutates at a rate 2-3 times lower than type A[14] and consequently is less genetically diverse, with only one influenza B serotype.[6] As a result of this lack of antigenic diversity, a degree of immunity to influenza B is usually acquired at an early age. However, influenza B mutates enough that lasting immunity is not possible.[15] This reduced rate of antigenic change, combined with its limited host range (inhibiting cross species antigenic shift), ensures that pandemics of influenza B do not occur.[16]
[edit] Influenza C Main article: Influenzavirus C

The influenza C virus infects humans and pigs, and can cause severe illness and local epidemics. [17] However, influenza C is less common than the other types and usually seems to cause mild disease in children.[18][19]

[edit] Virology

[edit] Morphology

Structure of the influenza virion. The hemagglutinin (HA) and neuraminidase (NA) proteins are shown on the surface of the particle. The viral RNAs that make up the genome are shown as red coils inside the particle and bound to Ribonuclear Proteins (RNPs).

The virion is pleomorphic, the envelope can occur in spherical and filamentous forms. In general the virus's morphology is spherical with particles 50 to 120 nm in diameter, or filamentous virions 20 nm in diameter and 200 to 300 (-3000) nm long. There are some 500 distinct spikelike surface projections of the envelope each projecting 10 to 14 nm from the surface with some types (i.e. hemagglutinin esterase (HEF)) densely dispersed over the surface, and with others (i.e. hemagglutinin (HA)) spaced widely apart. The major glycoprotein (HA) is interposed irregularly by clusters of neuraminidase (NA), with a ratio of HA to NA of about 4-5 to 1. Lipoprotein membranes enclose the nucleocapsids; nucleoproteins of different size classes with a loop at each end; the arrangement within the virion is uncertain. The nucleocapsids are filamentous and fall in the range of 50 to 130 nm long and 9 to 15 nm in diameter. They have a helical symmetry.
[edit] Genome

Viruses of this family contain 6 to 8 segments of linear negative-sense single stranded RNA.[20] The total genome length is 12000-15000 nucleotides (nt). The largest segment 2300-2500 nt; of second largest 2300-2500 nt; of third 2200-2300 nt; of fourth 1700-1800 nt; of fifth 1500-1600 nt; of sixth 1400-1500 nt; of seventh 1000-1100 nt; of eighth 800-900 nt. Genome sequence has terminal repeated sequences; repeated at both ends. Terminal repeats at the 5'-end 12-13 nucleotides long. Nucleotide sequences of 3'-terminus identical; the same in genera of same family; most on RNA (segments), or on all RNA species. Terminal repeats at the 3'-end 9-11 nucleotides long. Encapsidated nucleic acid is solely genomic. Each virion may contain defective interfering copies.
[edit] Structure For an in-depth example, see H5N1 genetic structure.

The following applies for Influenza A viruses, although other influenza strains are very similar in structure:[21] The influenza A virus particle or virion is 80-120 nm in diameter and usually roughly spherical, although filamentous forms can occur.[22] Unusually for a virus, the influenza A genome is not a single piece of nucleic acid; instead, it contains eight pieces of segmented negative-sense RNA (13.5 kilobases total), which encode 11 proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2).[23] The best-characterised of these viral proteins are hemagglutinin and neuraminidase, two large glycoproteins found on the outside of the viral particles. Neuraminidase is an enzyme involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles. By contrast, hemagglutinin is a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell.[24] The hemagglutinin (H) and neuraminidase (N) proteins are targets for antiviral drugs.[25] These proteins are also recognised by antibodies, i.e. they are antigens.[12] The responses of antibodies to these proteins are used to classify the different serotypes of influenza A viruses, hence the H and N in H5N1.
[edit] Life cycle

Invasion and replication of the influenza virus. The steps in this process are discussed in the text.

Typically, influenza is transmitted from infected mammals through the air by coughs or sneezes, creating aerosols containing the virus, and from infected birds through their droppings. Influenza can also be transmitted by saliva, nasal secretions, feces and blood. Infections occur through

contact with these bodily fluids or with contaminated surfaces. Flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0 C (32 F), and indefinitely at very low temperatures (such as lakes in northeast Siberia). They can be inactivated easily by disinfectants and detergents.[26][27][28] The viruses bind to a cell through interactions between its hemagglutinin glycoprotein and sialic acid sugars on the surfaces of epithelial cells in the lung and throat (Stage 1 in infection figure). [29] The cell imports the virus by endocytosis. In the acidic endosome, part of the haemagglutinin protein fuses the viral envelope with the vacuole's membrane, releasing the viral RNA (vRNA) molecules, accessory proteins and RNA-dependent RNA polymerase into the cytoplasm (Stage 2).[30] These proteins and vRNA form a complex that is transported into the cell nucleus, where the RNA-dependent RNA transcriptase begins transcribing complementary positive-sense cRNA (Steps 3a and b).[31] The cRNA is either exported into the cytoplasm and translated (step 4), or remains in the nucleus. Newly-synthesised viral proteins are either secreted through the Golgi apparatus onto the cell surface (in the case of neuraminidase and hemagglutinin, step 5b) or transported back into the nucleus to bind vRNA and form new viral genome particles (step 5a). Other viral proteins have multiple actions in the host cell, including degrading cellular mRNA and using the released nucleotides for vRNA synthesis and also inhibiting translation of host-cell mRNAs.[32] Negative-sense vRNAs that form the genomes of future viruses, RNA-dependent RNA transcriptase, and other viral proteins are assembled into a virion. Hemagglutinin and neuraminidase molecules cluster into a bulge in the cell membrane. The vRNA and viral core proteins leave the nucleus and enter this membrane protrusion (step 6). The mature virus buds off from the cell in a sphere of host phospholipid membrane, acquiring hemagglutinin and neuraminidase with this membrane coat (step 7).[33] As before, the viruses adhere to the cell through hemagglutinin; the mature viruses detach once their neuraminidase has cleaved sialic acid residues from the host cell.[29] After the release of new influenza virus, the host cell dies. Since RNA proofreading enzymes are absent, the RNA-dependent RNA transcriptase makes a single nucleotide insertion error roughly every 10 thousand nucleotides, which is the approximate length of the influenza vRNA. Hence, nearly every newly-manufactured influenza virus will contain a mutation in its genome.[34] The separation of the genome into eight separate segments of vRNA allows mixing (reassortment) of the genes if more than one variety of influenza virus has infected the same cell (superinfection). The resulting alteration in the genome segments packaged in to viral progeny confers new behavior, sometimes the ability to infect new host species or to overcome protective immunity of host populations to its old genome (in which case it is called an antigenic shift).[12]

[edit] Viability and disinfection

Mammalian influenza virus tend to be labile, but can survive several hours in mucus.[35] Avian influenza virus can survive for 100 days in distilled water at room temperature, and 200 days at 17 C (63 F). The avian virus is inactivated more quickly in manure, but can survive for up to 2 weeks in feces on cages. Avian influenza viruses can survive indefinitely when frozen.[35] Influenza viruses are susceptible to bleach, 70% ethanol, aldehydes, oxidizing agents, and

quaternary ammonium compounds. They are inactivated by heat of 133 F (56 C) for minimum of 60 minutes, as well as by low pH <2.[35]

[edit] Vaccination and Prophylaxis

Vaccines and drugs are, however, available for the prophylaxis and treatment of influenza virus infections. Vaccines are composed of either inactivated or live attenuated virions of the H1N1 and H3N2 human influenza A viruses as well as those of influenza B viruses. Because the antigenicities of the wild viruses evolve, vaccines are reformulated annually by updating the seed strains. However, when the antigenicities of the seed strains and wild viruses do not match, vaccines fail to protect the vaccinees. In addition, even when they do match, escape mutants are often generated. The drugs include amantadine, which inhibits the uncoating of virions by interfering with M2, and oseltamivir (marketed under the brand name Tamiflu), which inhibits the release of virions from infected cells by interfering with NA. However, escape mutants are often generated for the former drug and less frequently for the latter drug.[36]

Human respiratory syncytial virus

From Wikipedia, the free encyclopedia (Redirected from Respiratory syncytial virus)

Human respiratory syncytial virus

Classification and external resources

An x ray of a child with RSV showing the typical bilateral perifular fullness. ICD-10 B97.4

ICD-9 DiseasesDB MedlinePlus eMedicine MeSH

079.6 11387 001564 ped/2706 D018357

Human respiratory syncytial virus (RSV) is a virus that causes respiratory tract infections. It is the major cause of lower respiratory tract infections and hospital visits during infancy and childhood. A prophylactic medication (not a vaccine) exists for preterm birth (under 35 weeks gestation) infants and infants with a congenital heart defect (CHD) or bronchopulmonary dysplasia (BPD). Treatment is limited to supportive care, including oxygen therapy. In temperate climates there is an annual epidemic during the winter months. In tropical climates, infection is most common during the rainy season. In the United States, 60% of infants are infected during their first RSV season,[1] and nearly all children will have been infected with the virus by 23 years of age.[1] Of those infected with RSV, 23% will develop bronchiolitis, necessitating hospitalization.[2] Natural infection with RSV induces protective immunity which wanes over timepossibly more so than other respiratory viral infectionsand thus people can be infected multiple times. Sometimes an infant can become symptomatically infected more than once, even within a single RSV season. Severe RSV infections have increasingly been found among elderly patients. RSV is a negative-sense, single-stranded RNA virus of the family Paramyxoviridae, which includes common respiratory viruses such as those causing measles and mumps. RSV is a member of the paramyxovirus subfamily Pneumovirinae. Its name comes from the fact that F proteins on the surface of the virus cause the cell membranes on nearby cells to merge, forming syncytia.

Contents
[hide]

1 Signs and symptoms 2 Virology o 2.1 Transmission 3 Prevention 4 Treatment 5 See also 6 References 7 External links

[edit] Signs and symptoms

For most people, RSV produces only mild symptoms, often indistinguishable from common colds and minor illnesses. The Centers for Disease Control consider RSV to be the "most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia in children under 1 year of age in the United States".[3] For some children, RSV can cause bronchiolitis, leading to severe respiratory illness requiring hospitalization and, rarely, causing death. This is more likely to occur in patients that are immunocompromised or infants born prematurely. Other RSV symptoms common among infants include listlessness, poor or diminished appetite, and a possible fever.[4] Recurrent wheezing and asthma are more common among individuals who suffered severe RSV infection during the first few months of life than among controls;[5] whether RSV infection sets up a process that leads to recurrent wheezing or whether those already predisposed to asthma are more likely to become severely ill with RSV has yet to be determined. Symptoms of pneumonia in immuno-compromised patients such as in transplant patients and especially bone marrow transplant patients should be evaluated to rule out RSV infection. This can be done by means of PCR testing for RSV nucleic acids in peripheral blood samples if all other infectious processes have been ruled out or if it is highly suspicious for RSV such as a recent exposure to a known source of RSV infection.

[edit] Virology
Human respiratory syncytial virus

Transmission electron micrograph of RSV

Virus classification Group: Order: Family: Group V ((-)ssRNA) Mononegavirales Paramyxoviridae

RSV has 10 genes encoding 11 proteinsthere are 2 open reading frames of M2. NS1 and NS2 inhibit type I interferon activity. N encodes nucleocapsid protein that associates with the genomic RNA forming the nucleocapsid. M encodes the Matrix protein required for viral assembly. SH, G and F form the viral coat. The "G" protein is a surface protein that is heavily glycosylated. It functions as the attachment protein. The "F" protein is another important surface protein; F mediates fusion, allowing entry of the virus into the cell cytoplasm and also allowing the formation of syncytia. The "F" protein is homologous in both subtypes of RSV; antibodies directed at the "F" protein are neutralizing. In contrast, the "G" protein differs considerably between the two subtypes. M2 is the second matrix protein also required for transcription, it encodes M2-1 (elongation factor) and M2-2 (transcription regulation), M2 contains CD8 epitopes. L encodes the RNA polymerase. The phosphoprotein P is a cofactor for L. The atomic structure is now available for two of them, N[6] and M.[7] The genome is transcribed sequentially from NS1 to L with reduction in expression levels along its length
[edit] Transmission

RSV spreads easily by direct contact, and can remain viable for a half an hour or more on hands or for up to 5 hours on countertops.[8]

[edit] Prevention
As the virus is ubiquitous in all parts of the world, avoidance of infection is not possible. Epidemiologically, a vaccine would be the best answer. A vaccine trial in 1960s using a formalin-inactivated vaccine (FI-RSV), increased disease severity in children who had been vaccinated.[9] There is much active investigation into the development of a new vaccine, but at present no vaccine exists. Some of the most promising candidates are based on temperature sensitive mutants which have targeted genetic mutations to reduce virulence. However, palivizumab (brand name Synagis manufactured by MedImmune), a moderately effective prophylactic drug is available for infants at high risk. Palivizumab is a monoclonal antibody directed against RSV surface fusion protein. It is given by monthly injections, which are begun just prior to the RSV season and are usually continued for five months. RSV prophylaxis is indicated for infants that are premature or have either cardiac or lung disease, but the cost of prevention limits use in many parts of the world. An antiviral drugRibavirinis licensed for use, but its efficacy is limited.[10]

[edit] Treatment
Studies of nebulized hypertonic saline have shown that the "use of nebulized 3% HS is a safe, inexpensive, and effective treatment for infants hospitalized with moderately severe viral bronchiolitis" where "respiratory syncytial virus (RSV) accounts for the majority of viral bronchiolitis cases".[11][12] One study noted a 26% reduction in length of stay: 2.6 1.9 days, compared with 3.5 2.9 days in the untreated group (p=0.05).[11]

Supportive care includes fluids and oxygen until the illness runs its course. Salbutamol may be used in an attempt to relieve any bronchospasm if present. Increased airflow, humidified and delivered via nasal cannula, may be supplied in order to reduce the effort required for respiration. Adrenaline, bronchodilators, steroids, and ribavirin confer "no real benefit".[13][14]

Adenoviridae
From Wikipedia, the free encyclopedia (Redirected from Adenovirus) Adenoviruses

Transmission electron micrograph of two adenovirus particles

Virus classification Virus group: Group I (dsDNA) Family: Adenoviridae Genera

Atadenovirus Aviadenovirus Ichtadenovirus Mastadenovirus Siadenovirus Adenoviruses are medium-sized (90100 nm), nonenveloped (without an outer lipid bilayer) icosahedral viruses composed of a nucleocapsid and a double-stranded linear DNA genome. There are 57 described serotypes in humans, which are responsible for 510% of upper respiratory infections in children, and many infections in adults as well. Viruses of the family Adenoviridae infect various species of vertebrates, including humans. Adenoviruses were first isolated in 1953 from human adenoids. They are classified as group I under the Baltimore classification scheme, meaning their genomes consist of double stranded DNA.

Contents
[hide]

1 Virology o 1.1 Classification o 1.2 Diversity o 1.3 Structure o 1.4 Genome o 1.5 Replication 2 Epidemiology o 2.1 Transmission o 2.2 Humans o 2.3 Animals 3 Prevention 4 Infections 5 Treatment o 5.1 Utilization in treatment of unrelated diseases 6 See also 7 References 8 External links

[edit] Virology
[edit] Classification

This family contains the following genera:

Genus Genus Genus Genus AD-36 Genus

Atadenovirus; type species: Ovine adenovirus D Aviadenovirus; type species: Fowl adenovirus A Ichtadenovirus; type species: Sturgeon adenovirus A Mastadenovirus; type species: Human adenovirus C; others include Siadenovirus; type species: Frog adenovirus

[edit] Diversity

Classification of Adenoviridae can be complex. In humans, there are 57 accepted human adenovirus types (HAdV-1 to 57) in seven species (Human adenovirus A to G):[1]

A: 12, 18, 31 B: 3, 7, 11, 14, 16, 21, 34, 35, 50, 55 C: 1, 2, 5, 6, 57 [2]

D: 8, 9, 10, 13, 15, 17, 19, 20, 22, 23, 24, 25, 26, 27, 28, 29, 30, 32, 33, 36, 37, 38, 39, 42, 43, 44, 45, 46, 47, 48, 49, 51, 53, 54, 56[3] E: 4 F: 40, 41 G: 52[4]

Different types/serotypes are associated with different conditions:

respiratory disease (mainly species HAdV-B and C) conjunctivitis (HAdV-B and D) gastroenteritis (HAdV-F types 40, 41, HAdV-G type 52)

When not restricting the subject to human viruses, Adenoviridae can be divided into five genera: Mastadenovirus, Aviadenovirus, Atadenovirus, Siadenovirus, and Ichtadenovirus.[1]
[edit] Structure

Adenoviruses represent the largest nonenveloped viruses. Because of their large size, they are able to be transported through the endosome (i.e., envelope fusion is not necessary). The virion also has a unique "spike" or fiber associated with each penton base of the capsid (see picture below) that aids in attachment to the host cell via the coxsackie-adenovirus receptor on the surface of the host cell. In 2010, scientists announced that they had solved the structure of the human adenovirus at the atomic level, making the largest high-resolution model ever. The virus is composed of around 1 million amino acid residues and weighs around 150 MDa.[5][6]
[edit] Genome

Schematic diagram of the linear adenovirus genome, showing Early genes (E) and Late genes (L).

The adenovirus genome is linear, non-segmented double-stranded (ds) DNA that is between 26 and 45 Kbp. This allows the virus to theoretically carry 22 to 40 genes. Although this is significantly larger than other viruses in its Baltimore group, it is still a very simple virus and is

heavily reliant on the host cell for survival and replication. An interesting feature of this viral genome is that it has a terminal 55 kDa protein associated with each of the 5' ends of the linear dsDNA. These are used as primers in viral replication and ensure that the ends of the virus' linear genome are adequately replicated.
[edit] Replication

Adenoviruses possess a linear dsDNA genome and are able to replicate in the nucleus of mammalian cells using the hosts replication machinery.

The structure of adenovirus. 1 = penton capsomeres 2 = hexon capsomeres, and 3= viral genome (linear dsDNA)

Entry of adenoviruses into the host cell involves two sets of interactions between the virus and the host cell. Most of the action occurs at the vertices. Entry into the host cell is initiated by the knob domain of the fiber protein binding to the cell receptor. The two currently established receptors are: CD46 for the group B human adenovirus serotypes and the coxsackievirus adenovirus receptor (CAR) for all other serotypes. There are some reports suggesting MHC molecules and sialic acid residues functioning in this capacity as well. This is followed by a secondary interaction, where a specialized motif in the penton base protein interacts with an integrin molecule. It is the co-receptor interaction that stimulates internalization of the adenovirus. This co-receptor molecule is v integrin. Binding to v integrin results in endocytosis of the virus particle via clathrin-coated pits. Attachment to v integrin stimulates cell signaling and thus induces actin polymerization resulting in entry of the virion into the host cell within an endosome.[7] Once the virus has successfully gained entry into the host cell, the endosome acidifies, which alters virus topology by causing capsid components to disassociate. These changes as well as the toxic nature of the pentons result in the release of the virion into the cytoplasm. With the help of cellular microtubules, the virus is transported to the nuclear pore complex, whereby the adenovirus particle disassembles. Viral DNA is subsequently released, which can enter the nucleus via the nuclear pore.[8] After this the DNA associates with histone molecules. Thus, viral gene expression can occur and new virus particles can be generated. The adenovirus life cycle is separated by the DNA replication process into two phases: an early and a late phase. In both phases, a primary transcript that is alternatively spliced to generate

monocistronic mRNAs compatible with the hosts ribosome is generated, allowing for the products to be translated. The early genes are responsible for expressing mainly non-structural, regulatory proteins. The goal of these proteins is threefold: to alter the expression of host proteins that are necessary for DNA synthesis; to activate other virus genes (such as the virus-encoded DNA polymerase); and to avoid premature death of the infected cell by the host-immune defenses (blockage of apoptosis, blockage of interferon activity, and blockage of MHC class I translocation and expression). Some adenoviruses under specialized conditions can transform cells using their early gene products. E1a (binds Retinoblastoma tumor suppressor protein) has been found to immortalize primary cells in vitro allowing E1b (binds p53 tumor suppressor) to assist and stably transform the cells. Nevertheless, they are reliant upon each other to successfully transform the host cell and form tumors. DNA replication separates the early and late phases. Once the early genes have liberated adequate virus proteins, replication machinery, and replication substrates, replication of the adenovirus genome can occur. A terminal protein that is covalently bound to the 5 end of the adenovirus genome acts as a primer for replication. The viral DNA polymerase then uses a strand displacement mechanism, as opposed to the conventional Okazaki fragments used in mammalian DNA replication, to replicate the genome. The late phase of the adenovirus lifecycle is focused on producing sufficient quantities of structural protein to pack all the genetic material produced by DNA replication. Once the viral components have successfully been replicated, the virus is assembled into its protein shells and released from the cell as a result of virally induced cell lysis.

[edit] Epidemiology
[edit] Transmission

Adenoviruses are unusually stable to chemical or physical agents and adverse pH conditions, allowing for prolonged survival outside of the body and water. Adenoviruses are spread primarily via respiratory droplets, however they can also be spread by fecal routes as well.
[edit] Humans Main article: Adenovirus infection

Humans infected with adenoviruses display a wide range of responses, from no symptoms at all to the severe infections typical of Adenovirus serotype 14.
[edit] Animals See also: DA2PPC Vaccine

Two types of canine adenoviruses are well known, type 1 and 2. Type 1 causes infectious canine hepatitis, a potentially fatal disease involving vasculitis and hepatitis. Type 1 infection can also cause respiratory and eye infections. Canine adenovirus 2 (CAdV-2) is one of the potential causes of kennel cough. Core vaccines for dogs include attenuated live CAdV-2, which produces immunity to CAdV-1 and CAdV-2. CAdV-1 was initially used in a vaccine for dogs, but corneal edema was a common complication.[9] Adenovirus in Reptiles is poorly understood, but research is currently in progress. Adenoviruses are also known to cause respiratory infections in horses, cattle, pigs, sheep, and goats. Equine adenovirus 1 can also cause fatal disease in immunocompromised Arabian foals, involving pneumonia and destruction of pancreatic and salivary gland tissue.[9]

[edit] Prevention
Main article: Adenovirus vaccine

In the past, US military recruits were vaccinated against two serotypes of adenotypes, with a corresponding decrease in illnesses caused by those serotypes. The vaccine is no longer manufactured, and there are currently no vaccines available to protect against the adenovirus. The U.S. Army Medical Research and Materiel Command announced on 31 October 2011 that the new adenovirus vaccine, which replaces the older version that has been out of production for over a decade, was shipped to basic training sites Oct. 18, 2011. More information is available here. Good hygiene, including handwashing, is still the best way to avoid picking up the adenovirus from an infected person.

[edit] Infections
Main article: Adenovirus infection

Most infections with adenovirus result in infections of the upper respiratory tract. Adenovirus infections often show up as conjunctivitis, tonsilitis (which may look exactly like strep throat and cannot be distinguished from strep except by throat culture), an ear infection, or croup. Adenoviruses can also cause gastroenteritis (stomach flu). A combination of conjunctivitis and tonsilitis is particularly common with adenovirus infections. Some children (especially small ones) can develop adenovirus bronchiolitis or pneumonia, both of which can be severe. In babies, adenoviruses can also cause coughing fits that look almost exactly like whooping cough. Adenoviruses can also cause viral meningitis or encephalitis. Rarely, adenovirus can cause hemorrhagic cystitis (inflammation of the urinary bladdera form of urinary tract infection with blood in the urine).

Most people recover from adenovirus infections by themselves, but people with immunodeficiency sometimes die of adenovirus infections, and rarely even previously healthy people can die of these infections.[10] Adenoviruses are often transmitted by expectorate, but can also be transmitted by contact with an infected person, or by virus particles left on objects such as towels and faucet handles. Some people with adenovirus gastroenteritis may shed the virus in their stools for months after getting over the symptoms. The virus can be passed from one person to another through some sexual practices, and through water in swimming pools that do not have enough chlorine in them. As with many other illnesses, good handwashing is one way to lessen the spread of adenoviruses from one person to another. Heat and bleach will kill adenoviruses on objects.

[edit] Treatment
There are no antiviral drugs to treat adenoviral infections, so treatment is largely directed at the symptoms (such as acetaminophen for fever). A doctor may give antibiotic eyedrops for conjunctivitis, since it takes a while to test to see if the eye infection is bacterial or viral and to help prevent secondary bacterial infections.
[edit] Utilization in treatment of unrelated diseases

Adenovirus is used as a vehicle to administer targeted therapy,[11] in the form of recombinant DNA or protein. Specific modifications on fibre proteins are used to target Adenovirus to certain cell types;[12] a major effort is made to limit hepatotoxicity and prevent multiple organ failure. Adenovirus dodecahedron can qualify as a potent delivery platform for foreign antigens to human myeloid dendritic cells (MDC), and that it is efficiently presented by MDC to M1specific CD8+ T lymphocytes.[13]

Human parainfluenza viruses

From Wikipedia, the free encyclopedia (Redirected from Parainfluenza) Human parainfluenza viruses Virus classification Group: Order: Family: Group V ((-)ssRNA) Mononegavirales Paramyxoviridae

Human parainfluenza viruses

Classification and external

resources ICD-10 ICD-9 DiseasesDB MedlinePlus MeSH B34.8, J12.2, J20.4 480.2 30631 001370 D018184

Transmission electron micrograph of parainfluenza virus. Two intact particles and free filamentous nucleocapsid Human parainfluenza viruses (HPIVs) are a group of four distinct serotypes of enveloped single-stranded RNA viruses belonging to the paramyxovirus family.[1] Parainfluenza viruses can be detected via cell culture, immunofluorescent microscopy, and PCR.

Contents
[hide]

1 Clinical significance 2 Prevention 3 Types 4 Notes

[edit] Clinical significance

They are the second most common cause of lower respiratory tract infection in younger children. Together, the parainfluenza viruses cause ~75% of the cases of Croup. Repeated infection throughout the life of the host is not uncommon. Symptoms of later breakouts include upper respiratory tract illness as in a cold and sore throat. The incubation period of all

four serotypes is 1 to 7 days. In immunosuppressed people, such as transplant patients, parainfluenza virus infections can cause severe pneumonia, which can be fatal.[2]

[edit] Prevention
Though no vaccines currently exist, research is underway.[3] Parainfluenza viruses last only a few hours in the environment and are inactivated by soap and water.[4]

Herpes simplex virus

From Wikipedia, the free encyclopedia This article is about the virus. For information about the disease caused by the virus, see Herpes simplex. Herpes simplex virus

TEM micrograph of a herpes simplex virus.

Virus classification Group: Family: Group I (dsDNA) Herpesviridae

Subfamily: Alphaherpesvirinae Genus: Simplexvirus Species

Herpes simplex virus 1 (HSV-1) Herpes simplex virus 2 (HSV-2)

Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known as Human herpes virus 1 and 2 (HHV-1 and -2), are two members of the herpes virus family, Herpesviridae, that infect humans.[1] Both HSV-1 (which produces most cold sores) and HSV-2 (which produces most genital herpes) are ubiquitous and contagious. They can be spread when an infected person is producing and shedding the virus. Symptoms of herpes simplex virus infection include watery blisters in the skin or mucous membranes of the mouth, lips or genitals.[1] Lesions heal with a scab characteristic of herpetic disease. Sometimes, the viruses cause very mild or atypical symptoms during outbreaks. However, as neurotropic and neuroinvasive viruses, HSV-1 and -2 persist in the body by becoming latent and hiding from the immune system in the cell bodies of nerves. After the initial or primary infection, some infected people experience sporadic episodes of viral reactivation or outbreaks. In an outbreak, the virus in a nerve cell becomes active and is transported via the nerve's axon to the skin, where virus replication and shedding occur and cause new sores.[2]

Contents
[hide]

1 Transmission 2 Microbiology o 2.1 Viral structure o 2.2 Cellular entry o 2.3 Genetic inoculation o 2.4 Immune evasion o 2.5 Replication o 2.6 Latent infection 3 Viral genome 4 Treatment and vaccine development 5 Connection between facial sores and Alzheimer's disease 6 References 7 External links

[edit] Transmission
Main article: Herpes simplex

HSV-1 and -2 are transmitted from contact with an infectious area of the skin during reactivations of the virus. Although less likely, the herpes viruses can be transmitted during latency. Transmission is likely to occur during symptomatic reactivation of the virus that causes visible and typical skin sores. Asymptomatic reactivation means that the virus causes atypical, subtle or hard to notice symptoms that are not identified as an active herpes infection. Atypical symptoms are often attributed to other causes such as a yeast infection.[3][4] HSV-1 is usually

acquired orally during childhood, but may also be sexually transmitted. HSV-2 is primarily a sexually transmitted infection but rates of HSV-1 genital infections are increasing.[3] Both viruses may also be transmitted vertically during childbirth, although the real risk is very low.[5] The risk of infection is minimal if the mother has no symptoms or exposed blisters during delivery. The risk is considerable when the mother gets the virus for the first time during late pregnancy.[6] Symptoms resulting from primary infection with HSV are usually much more severe than subsequent outbreaks, as the body has not had a chance to produce antibodies. This first outbreak of oral herpes (cold sores) carries a low (1%) risk of developing aseptic meningitis.[1]

[edit] Microbiology
[edit] Viral structure

Animal herpes viruses all share some common properties. The structure of herpes viruses consists of a relatively large double-stranded, linear DNA genome encased within an icosahedral protein cage called the capsid, which is wrapped in a lipid bilayer called the envelope. The envelope is joined to the capsid by means of a tegument. This complete particle is known as the virion.[7] HSV-1 and HSV-2 each contain at least 74 genes (or open-reading frames, ORFs) within their genomes,[8] although speculation over gene crowding allows as many as 84 unique protein coding genes by 94 putative ORFs.[9] These genes encode a variety of proteins involved in forming the capsid, tegument and envelope of the virus, as well as controlling the replication and infectivity of the virus. These genes and their functions are summarized in the table below. The genomes of HSV1 and HSV2 are complex and contain two unique regions called the long unique region (UL) and the short unique region (US). Of the 74 known ORFs, UL contains 56 viral genes, whereas US contains only 12.[8] Transcription of HSV genes is catalyzed by RNA polymerase II of the infected host.[8] Immediate early genes, which encode proteins that regulate the expression of early and late viral genes, are the first to be expressed following infection. Early gene expression follows, to allow the synthesis of enzymes involved in DNA replication and the production of certain envelope glycoproteins. Expression of late genes occurs last; this group of genes predominantly encode proteins that form the virion particle.[8] Five proteins from (UL) form the viral capsid; UL6, UL18, UL35, UL38 and the major capsid protein UL19.[7]

[edit] Cellular entry

A simplified diagram of HSV replication

Entry of HSV into the host cell involves interactions of several glycoproteins on the surface of the enveloped virus, with receptors on the surface of the host cell. The envelope covering the virus particle, when bound to specific receptors on the cell surface, will fuse with the host cell membrane and create an opening, or pore, through which the virus enters the host cell. The sequential stages of HSV entry are analogous to those of other viruses. At first, complementary receptors on the virus and the cell surface bring the viral and cell membranes into proximity. In an intermediate state, the two membranes begin to merge, forming a hemifusion state. Finally, a stable entry pore is formed through which the viral envelope contents are introduced to the host cell.[10] In the case of a herpes virus, initial interactions occur when a viral envelope glycoprotein called glycoprotein C (gC) binds to a cell surface particle called heparan sulfate. A second glycoprotein, glycoprotein D (gD), binds specifically to at least one of three known entry receptors. These include herpesvirus entry mediator(HVEM), nectin-1 and 3O sulfated heparan sulfate. The receptor provides a strong, fixed attachment to the host cell. These interactions bring the membrane surfaces into mutual proximity and allow for other glycoproteins embedded in the viral envelope to interact with other cell surface molecules. Once bound to the HVEM, gD changes its conformation and interacts with viral glycoproteins H (gH) and L (gL), which form a complex. The interaction of these membrane proteins results in the hemifusion state. Afterward, gB interaction with the gH/gL complex creates an entry pore for the viral capsid.[10] Glycoprotein B interacts with glycosaminoglycans on the surface of the host cell.
[edit] Genetic inoculation

After the viral capsid enters the cellular cytoplasm, it is transported to the cell nucleus. Once attached to the nucleus at a nuclear entry pore, the capsid ejects its DNA contents via the capsid portal. The capsid portal is formed by twelve copies of portal protein, UL6, arranged as a ring;

the proteins contain a leucine zipper sequence of amino acids which allow them to adhere to each other.[11] Each icosahedral capsid contains a single portal, located in one vertex.[12][13] The DNA exits the capsid in a single linear segment.[14]
[edit] Immune evasion

HSV evades the immune system through interference with MHC class I presentation of antigen on the cell surface. It achieves this through blockade of the TAP transporter induced by the secretion of ICP-47[15] by HSV. TAP maintains the integrity of the MHC class I molecule before it is transported via the golgi apparatus for recognition by CD8+ CTLs on the cell surface. ICP47 disrupts this integrity, preventing the capture of cytosolic proteins for CTL recognition and thus evades CTL destruction.
[edit] Replication

Micrograph showing the viral cytopathic effect of HSV (multi-nucleation, ground glass chromatin).

Following infection of a cell, herpes virus proteins, called immediate-early, early, and late, are produced. Research using flow cytometry on another member of the herpes virus family, Kaposi's sarcoma-associated herpesvirus, indicates the possibility of an additional lytic stage, delayed-late.[16] These stages of lytic infection, particularly late lytic, are distinct from the latency stage. In the case of HSV-1, no protein products are detected during latency, whereas they are detected during the lytic cycle. The early proteins transcribed are used in the regulation of genetic replication of the virus. On entering the cell, an -TIF protein joins the viral particle and aids in immediate-early transcription. The virion host shutoff protein (VHS or UL41) is very important to viral replication.[17] This enzyme shuts off protein synthesis in the host, degrades host mRNA, helps in viral replication, and regulates gene expression of viral proteins. The viral genome immediately travels to the nucleus but the VHS protein remains in the cytoplasm.[18][19] The late proteins are used in to form the capsid and the receptors on the surface of the virus. Packaging of the viral particles including the genome, core and the capsid - occurs in the nucleus of the cell. Here, concatemers of the viral genome are separated by cleavage and are placed into pre-formed capsids. HSV-1 undergoes a process of primary and secondary

envelopment. The primary envelope is acquired by budding into the inner nuclear membrane of the cell. This then fuses with the outer nuclear membrane releasing a naked capsid into the cytoplasm. The virus acquires its final envelope by budding into cytoplasmic vesicles.[20]
[edit] Latent infection

HSVs may persist in a quiescent but persistent form known as latent infection, notably in neural ganglia.[1] HSV-1 tends to reside in the trigeminal ganglia, while HSV-2 tends to reside in the sacral ganglia, but note that these are tendencies only, not fixed behavior. During such latent infection of a cell, HSVs express Latency Associated Transcript (LAT) RNA. LAT is known to regulate the host cell genome and interferes with natural cell death mechanisms. By maintaining the host cells, LAT expression preserves a reservoir of the virus, which allows subsequent, usually symptomatic, periodic recurrences or "outbreaks" characteristic of non-latency. Whether or not recurrences are noticeable (symptomatic) or not, viral shedding occurs to produce further infections (usually in a new host, if any). A protein found in neurons may bind to herpes virus DNA and regulate latency. Herpes virus DNA contains a gene for a protein called ICP4, which is an important transactivator of genes associated with lytic infection in HSV-1.[21] Elements surrounding the gene for ICP4 bind a protein known as the human neuronal protein Neuronal Restrictive Silencing Factor (NRSF) or human Repressor Element Silencing Transcription Factor (REST). When bound to the viral DNA elements, histone deacetylation occurs atop the ICP4 gene sequence to prevent initiation of transcription from this gene, thereby preventing transcription of other viral genes involved in the lytic cycle.[21][22] Another HSV protein reverses the inhibition of ICP4 protein synthesis. ICP0 dissociates NRSF from the ICP4 gene and thus prevents silencing of the viral DNA.[23] The virus can be reactivated by illnesses such as colds and influenza, eczema, emotional and physical stress, gastric upset, fatigue or injury, by menstruation and possibly exposure to bright sunlight.

[edit] Viral genome

The open reading frames (ORFs) of HSV-1[8][24]
Gen e UL1

Protein

Function/description

Gen e

Protein Function/description
Capsid assembly and DNA maturation Ribonucleotide reductase (Large subunit) Ribonucleotide reductase (Small subunit) Tegument protein; Virion host shutoff[17]

Glycoprotei Surface and membrane n L [1] Uracil-DNA glycosylase

UL3 UL38; 8 VP19C [2] UL3 UL39 [4] 9 UL4 UL40 [6] 0 UL4 UL41; VHS 1 [8] UL4 UL42 [10] 2

UL2 UL2 [3]

UL3 UL3 [5]

unknown

UL4 UL4 [7]

unknown

UL5 UL5 [9]

DNA replication

DNA polymerase processivity factor

Twelve of these proteins constitute Portal the capsid portal ring through UL4 UL6 UL43 [11] protein UL-6 which DNA enters and exits the 3 [11][12][13] capsid. UL7 UL7 [12] Virion maturation DNA helicase/primase complexassociated protein Replication origin-binding protein

Membrane protein

UL4 Glycoprotei Surface and membrane 4 n C [13] UL4 UL45 [15] 5 Membrane protein; C-type lectin[25]

UL8 UL8 [14]

UL9 UL9 [16]

UL4 VP11/12 Tegument proteins 6 [17] UL47; UL4 VP13/14 7 [19]

UL1 Glycoprotei Surface and membrane 0 n M [18]

Tegument protein

UL1 UL11 [20] 1

virion exit and secondary envelopment

Virion maturation; activate IEGs by VP16 UL4 interacting with the cellular (Alpha-TIF) 8 transcription factors Oct-1 and HCF. [21] Binds to the sequence 5'TAATGARAT3'. UL4 UL49A [23] Envelope protein 9 UL5 UL50 [25] 0 UL5 UL51 [27] 1 UL5 UL52 [29] 2 dUTP diphosphatase

UL1 UL12 [22] 2 UL1 UL13 [24] 3 UL1 UL14 [26] 4 UL1 Terminase 5 [28] UL1 UL16 [30] 6 UL1 UL17 [32] 7 UL1 VP23 [34] 8 UL1 VP5 [36] 9 UL2 UL20 [38] 0 UL2 UL21 [40] 1

Alkaline exonuclease

Serine-threonine protein kinase

Tegument protein

Tegument protein

Processing and packaging of DNA

DNA helicase/primase complex protein

Tegument protein

UL5 Glycoprotei Surface and membrane 3 n K [31] UL5 IE63; ICP27 Transcriptional regulation 4 [33] UL5 UL55 [35] 5 UL5 UL56 [37] 6 US1 Unknown

Processing and packaging DNA

Capsid protein

Major capsid protein

Unknown

Membrane protein

ICP22; IE68 Viral replication [39] Unknown

Tegument protein[26]

US2 US2 [41]

UL2 Glycoprotei Surface and membrane 2 n H [42] UL2 Thymidine Peripheral to DNA replication 3 kinase [44] UL2 UL24 [46] 4 UL2 UL25 [48] unknown Processing and packaging DNA

US3 US3 [43]

Serine/threonine-protein kinase

US4

Glycoprotei Surface and membrane n G [45] Glycoprotei Surface and membrane n J [47]

US5

US6 Glycoprotei Surface and membrane

5 UL2 P40; VP24; Capsid protein 6 VP22A [50] UL2 Glycoprotei Surface and membrane 7 n B [52] UL2 ICP18.5 [54] Processing and packaging DNA 8 UL2 UL29; ICP8 9 [56] Major DNA-binding protein US7

n D [49] Glycoprotei Surface and membrane n I [51] Glycoprotei Surface and membrane n E [53] Tegument protein

US8

US9 US9 [55] US1 US10 [57] 0

Capsid/Tegument protein

DNA UL3 polymerase DNA replication 0 [58] UL3 UL31 [60] 1 Nuclear matrix protein

US1 US11; Binds DNA and RNA 1 Vmw21 [59] US1 ICP47; IE12 Inhibits MHC class I pathway by 2 [61] preventing binding of antigen to TAP Major transcriptional activator. ICP4; IE175 Essential for progression beyond the RS1 [63] immediate-early phase of infection. IEG transcription repressor. E3 ubiquitin ligase that activates viral ICP0; IE110; gene transcription and counteracts the 0 [65] interferon response Latency-related protein

UL3 UL32 [62] 2

Envelope glycoprotein

UL3 UL33 [64] 3 UL3 UL34 [66] 4 UL3 VP26 [68] 5 UL3 UL36 [70] 6 UL3 UL37 [72] 7

Processing and packaging DNA

ICP0

Inner nuclear membrane protein

LRP LRP1 [67] 1 LRP LRP2 [69] 2 RL1

Capsid protein

Latency-related protein

Large tegument protein

RL1; Neurovirulence factor. Antagonizes PKR ICP34.5 [71] by de-phosphorylating eIF4a. Latency-associated transcript

Capsid assembly

LAT none [73]

[edit] Treatment and vaccine development

For more details on treatment of herpes simplex virus, see Herpes simplex. For more information on vaccines, see Herpes simplex vaccine

Herpes viruses establish lifelong infections and the virus cannot currently be eradicated from the body. Treatment usually involves general-purpose antiviral drugs that interfere with viral replication, reducing the physical severity of outbreak-associated lesions and lowering the chance of transmission to others. Studies of vulnerable patient populations have indicated that daily use of antivirals such as acyclovir and valacyclovir can reduce reactivation rates.[4] In vitro research has indicated that Aloe Vera may be effective against genital herpes.[27]

[edit] Connection between facial sores and Alzheimer's disease

In the presence of a certain gene variation (APOE-epsilon4 allele carriers), a possible link between HSV-1 (i.e., the virus that causes cold sores or oral herpes) and Alzheimers disease was reported in 1979.[28] HSV-1 appears to be particularly damaging to the nervous system and increases ones risk of developing Alzheimers disease. The virus interacts with the components and receptors of lipoproteins, which may lead to the development of Alzheimer's disease.[29] This research identifies HSVs as the pathogen most clearly linked to the establishment of Alzheimers.[30] Without the presence of the gene allele, HSV-1 does not appear to cause any neurological damage or increase the risk of Alzheimers.[31] Many more Alzheimer's disease susceptibility genes, including the major players APOE, clusterin, complement receptor 1 and PICALM are involved in the herpes simplex life cycle as curated in this database

Cytomegalovirus
From Wikipedia, the free encyclopedia This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (June 2007)

Cytomegalovirus
ICD-10 ICD-9 MeSH Classification and external resources B25 078.5 D003586 Cytomegalovirus

CMV infection of a lung pneumocyte.

Virus classification Group: Group I (dsDNA) Family: Herpesviridae Subfamily: Betaherpesvirinae Genus: Cytomegalovirus Species

see text Cytomegalovirus (from the Greek cyto-, "cell", and -megalo-, "large") is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV (HCMV) or human herpesvirus-5 (HHV-5), and is the most studied of all cytomegaloviruses.[1] Within Herpesviridae, CMV belongs to the Betaherpesvirinae subfamily, which also includes the genera Muromegalovirus and Roseolovirus.[2] It is related to other herpesviruses within the subfamilies of Alphaherpesvirinae that includes herpes simplex viruses (HSV)-1 and -2 and varicella-zoster virus (VZV), and the Gammaherpesvirinae subfamily that includes EpsteinBarr virus.[1] All herpesviruses share a characteristic ability to remain latent within the body over long periods. Although they may be found throughout the body, CMV infections are frequently associated with the salivary glands in humans and other mammals.[2] Other CMV viruses are found in several mammal species, but species isolated from animals differ from HCMV in terms of genomic structure, and have not been reported to cause human disease.

[edit] Species
Classified Cytomegaloviruses Scientific Name Host Human herpesvirus 5 (HHV-5) Human Cercopithecine herpesvirus 5 (CeHV-5) African green Cercopithecine herpesvirus 8 (CeHV-8) monkey Panine herpesvirus 2 (PaHV-2) Rhesus monkey Pongine herpesvirus 4 (PoHV-4) Chimpanzee Aotine herpesvirus 1 (AoHV-1) - tentative Orangutan classification Night monkey Aotine herpesvirus 3 (AoHV-3) - tentative " classification Common Name Human CMV (HCMV) Simian CMV (SCCMV) Rhesus CMV (RhCMV) Chimpanzee CMV (CCMV) " Herpesvirus aotus 1 Herpesvirus aotus 3

Several species of cytomegalovirus have been identified and classified for different mammals.[2] The most studied is human CMV (HCMV), which is also known as human herpesvirus-5 (HHV5). Other primate CMV species include chimpanzee CMV (CCMV) that infects chimpanzees and orangutans, and simian CMV (SCCMV) and rhesus CMV (RhCMV) that infect macaques; CCMV is known as both panine herpesvirus-2 (PaHV-2) and pongine herpesvirus-4 (PoHV-4), SCCMV is also called cercopithecine herpesvirus-5 (CeHV-5) and RhCMV is also called cercopithecine herpesvirus-8 (CeHV-8). A further two viruses found in the night monkey are tentatively placed in the cytomegalovirus genus, and are called Herpesvirus aotus 1 and Herpesvirus aotus 3. Rodents also have viruses previously called cytomegaloviruses that are now reclassified under the genus muromegalovirus; this genus contains mouse CMV (MCMV) is also known as murid herpesvirus 1 (MuHV-1) and the closely related murid herpesvirus 2 (MuHV-2) that is found in rats. In addition, there many other viral species with the name cytomegalovirus identified in distinct mammals that are as yet not completely classified; these were predominantly isolated from primates and rodents.

[edit] HCMV

Main article: human cytomegalovirus Human cytomegalovirus is a species of virus that belongs to the viral family known as Herpesviridae or herpesviruses. It is typically abbreviated as HCMV and is alternatively known as human herpesvirus-5 (HHV-5).[1] Within Herpesviridae, HCMV belongs to the Betaherpesvirinae subfamily, which also includes cytomegaloviruses from other mammals.[2] Although they may be found throughout the body, HCMV infections are frequently associated with the salivary glands.[2] HCMV infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised, such as HIV-infected persons, organ transplant recipients, or new born infants.[1] After infection, HCMV has an ability to remain latent within the body over long periods. HCMV is found throughout all geographic locations and socioeconomic groups, and infects between 50% and 80% of adults in the United States (40% worldwide[3]) as indicated by the presence of antibodies in much of the general population.[1] Seroprevalence is age-dependent: 58.9% of individuals aged 6 and older are infected with CMV while 90.8% of individuals aged 80 and older are positive for HCMV.[4] HCMV is also the virus most frequently transmitted to a developing fetus. HCMV infection is more widespread in developing countries and in communities with lower socioeconomic status and represents the most significant viral cause of birth defects in industrialized countries. CMV "seems to have a large impact on immune parameters in later life and may contribute to increased morbidity and eventual mortality."[5]