1

Enveloped RNA Viruses

Review ............................................................................................................................................2

Segmented, Single-Stranded, Negative-Sense Genome Orthomyxoviridae: Inuenza A, B and C

Properties of Orthomyxoviruses .............................................................................................6 Epidemiology of Inuenza A ....................................................................................................8 Community Immunity, Genetic Change and Inuenza ...........................................................9 Stages in cell invasion and disruption ..................................................................................11 Infection and Disease ..............................................................................................................12 Diagnosis, Treatment and Prevention of Inuenza ..............................................................13

Nonsegmented, Single-Stranded, Negative-Sense Genome Paramyxoviridae Rhabdoviridae Filoviridae Single-Stranded, Positive-Sense, Reverse Transcriptase Retroviridae AIDS (HIV)
Introduction for Retroviridae ...............................................................................................53 Biology of the Retroviruses ................................................................................................54 Structure and Behavior of Retroviruses ............................................................................55 Historical Background of AIDS ...........................................................................................56 Origin of AIDS ......................................................................................................................57 Epidemiology of AIDS ..........................................................................................................58 Clinical Denition of AIDS ...................................................................................................59 Case Descriptions According to Group, in order of prevalence .......................................60 Modes of Transmission .......................................................................................................62 Misconceptions: How AIDS is NOT Transmitted ..............................................................63

AIDS Pathology
Initial Infection of Target Cells ..........................................................................................65 Stages of HIV Infection and Disease ................................................................................67 The Primary Effects: Harm to T-cells and the Brain .......................................................68 Secondary Effects That Dene AIDS ................................................................................69 Effects of Co-infection ......................................................................................................71 Testing for HIV ......................................................................................................................72 AIDS Therapy .......................................................................................................................73 AIDS Protection ....................................................................................................................75 Will There Be an AIDS Vaccine? .........................................................................................76

Other Retroviral Diseases in Humans

Adult T-cell Leukemia (ATL) ................................................................................................78 Hairy-cell Leukemia (HCL) ...................................................................................................79

Review
Nucleocapsid Helical: ribbonlike protein that forms a spiral around the nucleic acid

Icosahedral: has 20 triangular faces

Genome Strandedness Single-Stranded

Double-Stranded

Number of molecules Segmented Nonsegmented

Sense Postive-Sense -if the RNA of the virus is in a form ready to be translated by the host's ribosomes

Negative-Sense

Negative-Sense -it is not directly translatable by the host -the RNA acts as a template during transcription to make a complementary (+) sense mRNA -this new (+) sense RNA is now translated by the host's ribosomes -in order to perform the transcription step, negative-sense RNA viruses must carry an RNA polymerase within the virion

Segmented, Single-Stranded, Negative-Sense Genome

Orthomyxoviridae: Inuenza A, B and C
Properties of Orthomyxoviruses ...............................................................................................6 Epidemiology of Inuenza A ......................................................................................................8 Community Immunity, Genetic Change and Inuenza .............................................................9 Stages in cell invasion and disruption .....................................................................................11 Infection and Disease ................................................................................................................12 Diagnosis, Treatment and Prevention of Inuenza ................................................................13

Orthomyxoviridae: Inuenza A, B and C

Properties of Orthomyxoviruses ..................................................................................................6 Epidemiology of Inuenza A .........................................................................................................8 Community Immunity, Genetic Change and Inuenza ...............................................................9 Stages in cell invasion and disruption .......................................................................................11 Infection and Disease ...................................................................................................................12 Diagnosis, Treatment and Prevention of Inuenza ...................................................................13

Properties of Orthomyxoviruses
major cause of mortality and morbidity in respiratory illnesses major cause of outbreaks of infection in worldwide epidemics 3 immunologic types of inuenza virus 1. Inuenza A -antigen changes continually within this group -high antigen variability -responsible for most cases of epidemic inuenza -aside from humans, this strain in also known in aquatic birds, chickens, ducks, pigs, horses and seals 2. Inuenza B -has a high antigen variability but to a lesser degree 3. Inuenza C -antigenically stable Properties

Properties Virion: enveloped, spherical, average diameter of 80-120nm, nucleocapsid is helical Genome: single-stranded RNA, segmented (8 molecules), negative-sense, 13.6 kb overall size Envelope: -lipoprotein in nature -studded with glycoprotein spikes that is acquired during viral maturation 2 proteins that make up the spikes of the envelope -contribute to the virulence of the organism a) hemagglutinin (HA) -combines with a specic carbohydrate molecule found in all eukaryotic cell membranes -gives the virus the capacity to bind and clump a variety of animal cells -it has a particular agglutinating action on red blood cells -this is the basis for viral assays used to identify several antigenic types -contribute to the infectivity of the virus -by binding to host cell receptors of the respiratory mucosa b) neuraminidase (NA) -principal action: hydrolyze the protective mucous coating of the respiratory tract -assist in viral budding and release -keep the viruses from sticking together -participate in host cell fusion

Genetic reassortment -the genome is segmented -when a cell is coinfected by two different viruses of a given type, mixture of the parental genes may be assembled into progeny virions -this may result in a sudden change in the viral surface antigenic property -explains the epidemiologic features of inuenza -poses signicant problems in vaccine development Pattern of antigenic change can be grouped based on its degree and timing of change A. Antigenic shift -a major alteration in antigenicity -occurs when genome segments from different viral strains recombine -a whole new strain can emerge in a single recombinant event -ex. when a human is simultaneously infected by both a human and an animal strain of the virus B. Antigenic drift -a minor change in antigenicity -caused by a small mutations in a single virus strain -antigenic variations accumulate over time -a new viral strain is produced

Epidemiology of Inuenza A
-an acute infection -highly contagious respiratory illness -aficts people of all ages -marked by seasonal regularity and pandemics at regular interval inuenza A -the most virulent type -most commonly associated with human disease naming of inuenza -inuenza virus type, the presumed animal of origin, the location and year of origin -ex. -inuenza A/duck/Ukraine/63 -inuenza A/seal/Mass/80 -"swine ue", "HongKong u" mode of transmission major route: inhalation of virus-laden aerosols and droplets secondary route: through fomites factors that facilitate transmission -crowding -poor ventilation mortality rate: 0.1% of cases -common among elderly and small children etiology of the name -from an Italian phrase -un inuenza di freddo: an "inuence of mystery" -has been shortened to the term "u"

Community Immunity, Genetic Change and Inuenza

Community immunity -herd immunity -collective resistance of individuals in a population -achieved by active infection, vaccination and transplacental body transfer -most effective: 1. when the virus has recently pass through a population -least effective: 1. when a new virus strain appears 2. when a new virus strain is imported from another population Inuenza viruses undergo genetic variation and antigenic change. Viral components most subject to change: -hemagglutinin spikes -neuraminidase spikes These 2 structures -determine infectivity -induce protective antibodies Accumulated changes can create variants that are antigenically different. -antibodies from previous infection is no longer protective -results in: -lapses in individual immunity -lapses in herd immunity -epidemics Antigenic shift -there is an increased possibility when: -there is simultaneously infection of one individual by 2 different inuenza strains -ex. bird strain and a swine strain -give rise to a completely new viral strain different from either original -if the new altered strain introduced into either animal or human population -it will spread rapidly -neither group has protective antibodies Factors that facilitate inuenza pandemics 1. high degree of contagiousness 2. widespread migration or travel In theory: 256 different genome combinations -inuenza has 8 genome -28 is 256

Stages in cell invasion and disruption

Infection and Disease

Infection -binding of the inuenza virus to ciliated cells of the respiratory mucosa -rapid shedding of these cells along with a load of viruses -elimination of the ciliary clearance -leads to severe inammation and irritation -SSx: -fever -headache -myalgia -pharyngeal pain -shortness of breath -repetitive bouts of coughing -viruses remain in the respiratory tract: viremia is rare -the ciliated columnar epithelium is restored in 1-2 weeks: symptoms usually subside Populations susceptible to severe complications -patients with emphysema or cardiopulmonary disease -the very young -the elderly -pregnant patients They have weakened host defenses. -predisposed to secondary bacterial infections: pneumonia -Streptococcus pneumoniae -Staphylococcus aureus Complications of inuenza infection -pneumonia -bronchitis -meningitis -neuritis

10

Diagnosis, Treatment and Prevention of Inuenza

Diagnosis 1. Rapid Immunouorescence test -detect inuenza antigens in a pharyngeal specimen

2. Serologic testing -screen for antibody titer 3. Virus isolation -in chick embryos -in kidney cell culture 4. Genetic analysis -determining the origin of the virus Treatment 1. supportive measure: to control the symptoms -uids -bed rest -nonaspirin pain relievers and anti-inammatory drugs Aspirin -not indicated -it signicantly increases the risk for Reye syndrome -a disease that involves the brain, liver and kidney -fatty degeneration of these organs 2. amantadine and rimantadine -specically block the uncoating of the inuenza virus in the cell -given to abate the course of severe inuenza -if given early, it can reduce: -the length of the disease -the symptoms of the disease -the spread of the virus -disadvantage: CNS toxicity - so use with caution Prevention Vaccination -vaccine

Prevention Vaccination -vaccine 1. contains dead viruses grown in embryonated eggs -injected subcutaneously -overall effectiveness: 70-90% 2. an attenuated vaccine -given intranasally -appears to be more effective -requires smaller doses indications for inuenza vaccination -for high-risk groups -chronically ill -elderly -people with high degree of exposure to the public Sequelae associated with inuenza vaccines -Guillain-Barre syndrome -a neurological complication -1/100,000 vaccine recipients -appears to be an autoimmune disease induced by the viral proteins -marked by varying degree of demyelination of the PNS -weakness and sensory loss -most patients recover function -it can also be debilitating and fatal

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Nonsegmented, Single-Stranded, Negative-Sense Genome

Paramyxoviridae
Introduction ...............................................................................................................................17 Parainuenza ............................................................................................................................19

Mumps Virus
Mumps: Epidemic Parotitis ...................................................................................................21 Epidemiology and Pathology ................................................................................................22 Complication ...........................................................................................................................23 Diagnosis, Treatment and Prevention of Mumps .................................................................24

Measles Virus
Introduction to Measles: Morbillivirus Infection ..................................................................26 Epidemiology of Measles .......................................................................................................27 Infection, Disease and Complications of Measles ...............................................................28 Diagnosis, Treatment and Prevention of Measles ................................................................30

Respiratory Syncytial Virus

Introduction to Respiratory Syncytial Virus or RSV infection .............................................32 Symptoms, Pathogenesis ......................................................................................................33 Diagnosis, Prevention and Treatment ...................................................................................34

Rhabdoviridae Rabies virus

Introduction ............................................................................................................................37 Epidemiology of Rabies .........................................................................................................38 Infection and Disease .............................................................................................................39 Clinical Phases of Rabies ......................................................................................................40 Diagnosis of Rabies ...............................................................................................................41 Rabies Management, Prevention and Control ......................................................................42

Filoviridae
Introduction ...............................................................................................................................44 Transmission of EBOV and MARV ...........................................................................................45 Viral Structure and Composition .............................................................................................46 Clinical Features/Presentation .................................................................................................47 Host Response ..........................................................................................................................48 Treatment and Prevention ........................................................................................................49

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Paramyxoviridae
Introduction .................................................................................................................................17 Parainuenza ...............................................................................................................................19

Mumps Virus
Mumps: Epidemic Parotitis .....................................................................................................21 Epidemiology and Pathology ...................................................................................................22 Complication .............................................................................................................................23 Diagnosis, Treatment and Prevention of Mumps ...................................................................24

Measles Virus
Introduction to Measles: Morbillivirus Infection .....................................................................26 Epidemiology of Measles .........................................................................................................27 Infection, Disease and Complications of Measles ..................................................................28 Diagnosis, Treatment and Prevention of Measles ..................................................................30

Respiratory Syncytial Virus

Introduction to Respiratory Syncytial Virus or RSV infection ...............................................32 Symptoms, Pathogenesis ........................................................................................................33 Diagnosis, Prevention and Treatment .....................................................................................34

13

Introduction
Paramyxoviruses -nonsegmented, single-stranded, negative-sense

Important human paramyxoviruses 1. Paramyxovirus -parainuenza virus -mumps virus 2. Morbillivirus -measles virus 3. Pneumovirus -respiratory syncytial virus Mode of transmission: inhalation of respiratory droplets Structure: -envelope of the paramyxoviruses possesses 1. HN spikes 2. F glycoproteins spikes

The cell membrane of an infected cell is modied by the insertion of the spikes. HN spikes -bind an uninfected neighboring cell F glycoprotein spikes -causes the 2 cells to fuse permanently Multiple cell fusions produce a syncytium or a multinucleate giant cell with cytoplasmic inclusion bodies. -this cytopathic effect is diagnostically useful.

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Parainuenza
Epidemiology and Pathology -as widespread as inuenza -usually more benign -modes of infection a) inhalation of droplets and respiratory secretions b) inoculation into the mucous membranes by contaminated hands -individuals affected -most frequent in children -most are infected by the age of 6 -babies lacking passive antibodies -develop more severe symptoms -SSx -minor upper respiratory symptoms -colds -bronchitis -bronchopneumonia -laryngotracheobronchitis (croup) -labored and noisy breathing -a hoarse cough -common in infants and young children Diagnosis, Treatment and Prevention -presenting symptoms typical of a cold--> presume that it is of viral origin -determining the actual viral agent -difcult -not necessary in older children and adults -infection is usually self-limiting and benign -primary infection in infants can be severe and life-threatening -there is no specic chemotherapy available -supportive measure -immune serum globulin or interferon could be benecial

15

Mumps Virus
Mumps: Epidemic Parotitis .......................................................................................................21 Epidemiology and Pathology .....................................................................................................22 Complication ...............................................................................................................................23 Diagnosis, Treatment and Prevention of Mumps ......................................................................24

16

Mumps: Epidemic Parotitis

-caused by Paramyxovirus -old English for lump or bump -described by Hippocrates -self-limited, mildly epidemic illness -associated w/ painful swelling at the angle of the jaw -also called epidemic parotitis -targets the parotid salivary glands -not limited to this region -bears morphological and antigenic resemblance to parainuenza -has only a single serologic type

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Epidemiology and Pathology

Humans -exclusive natural hosts Mode of infection -through salivary and respiratory secretions Distribution: worldwide -increase in epidemics in the late winter and early spring in temperate climates High rates of infection -among crowded populations -communities with poor herd immunity Most occur in children under 15 years old. -40% subclinical No long term carrier reservoir exists in the population. -lasting immunity follows any form of mumps infection. Incidence US data: 300 cases/year Incubation period -2-3 weeks Initial symptoms -fever -nasal discharge -muscle pain -malaise Inammation of the salivary glands -parotids -classic gopherlike swelling of the cheeks on one or both sides -swelling of the ducts and glands Viral multiplication -occurs in the salivary glands -followed by invasion of other organs -testes, ovaries, thyroid gland, pancreas, meninges, heart and kidney Prognosis -complete, uncomplicated recovery -with permanent immunity

18

Complication
Orchitis and epididymitis -in 20-30% of young adult males -localization of the mumps infection in the testis and epididymis -usually on one side only -painful but no permanent damage occurs -popular belief: sterilization of adult males -tenderness that continues after the infection -partial atrophy of the testis in 50% of cases -permanent sterility due to mumps is very rare Mumps pancreatitis -mumps virus replicates in beta cells and pancreatic epithelial cells Viral meningitis -fever, headache and stiff neck -appears 2-10 days after the onset of parotitis -lasts for 3-5 days -leaves no or few adverse side effects Infection of the inner ear -leads to deafness

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Diagnosis, Treatment and Prevention of Mumps

Diagnosis -tentative diagnosis -swollen parotid glands in a child -known exposure 2-3 weeks prior -may sometimes be missed -parotitis is not always present -incubation period may range from 7-23 days -more practical diagnostic tests 1. Direct Fluorescent test -detect viral antigen 2. ELISA -detect antigen or antibodies on the serum

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Measles Virus
Introduction to Measles: Morbillivirus Infection .......................................................................26 Epidemiology of Measles ............................................................................................................27 Infection, Disease and Complications of Measles ....................................................................28 Diagnosis, Treatment and Prevention of Measles ....................................................................30

21

Introduction to Measles: Morbillivirus Infection

other names: -red measles, origin of the word -Dutch word "maselen" --> spotted -rubeola, origin of the word -Latin word "rubor" -->red German measles (rubella) -another disease entity -an entirely unrelated viral infection

eighth most frequent cause of death worldwide

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Epidemiology of Measles
transmission -by respiratory aerosols factors that favor epidemic spread -crowding -low levels of herd immunity -malnutrition -inadequate medical care -lack of immunization -failure of a single dose of vaccine Humans: the only reservoir Infectious stage: -incubation period -prodromal stage -period of skin rash Not infectious during the convalescence period.

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Infection, Disease and Complications of Measles

During the incubation period -about 2 weeks -virus invades the mucosal lining of the RT Initial symptoms -sore throat, dry cough, headache, conjuctivitis -coryza, lymphadenitis, and fever Koplik spots -oral lesions pathognomonic for measles -clustered white lesions on the buccal mucosa -opposite the premolars -appears like "grains of salt on a wet background" -appears about 2 days before the exanthem appears

Measles exanthem -red and maculopapular -erupts on the head rst -progresses to the trunk and extremities until most of the body is covered -rashes gradually coalesces into red patches -fades to a brown color Complications -laryngitis -bronchopneumonia -other secondary bacterial infections -otitis media -sinusitis -severe diarrhea and abdominal discomfort in undernourished children -SSPE -subacute sclerosing panencephalitis -most serious complication -a progressive neurological degeneration of the cerebral cortex, white matter and the brain stem -incidence: 1/1,000,000 cases -aficts primarily male children and adolescents -pathogenesis: -a defective virus -it has lost its capability to form a capsid -it is not released from the infected cell -it spreads unchecked through the brain by cell fusion -gradually destroys neurons and accessory cells -it breaks down myelin -manifestation: -intellectual and neurological impairment -lead to coma and death in a matter of months or

-manifestation: -intellectual and neurological impairment -lead to coma and death in a matter of months or years

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Diagnosis, Treatment and Prevention of Measles

Epidemiological clues for the diagnosis of measles -patient's age -history of recent exposure to measles Clinical characteristics of measles -dry cough, sore throat, coryza, conjunctivitis, lymphadenopathy and fever -appearance of Koplik spots -appearance of the characteristic rash Treatment -supportive measures -reduce the fever -suppress the cough -replace lost uids -for the complications -relieve neurological and respiratory symptoms -sustain the nutrition, electrolytes and uid levels -antibiotics for the secondary bacterial infection -immune globulin Prevention -Vaccination:

-attenuated viral vaccine -injected subcutaneously -persists for 20 years -it can cause an atypical infection sometimes -rash and fever -becaause the vaccine is live -measles immunization: at 9 months -MMR: rst dose at 12-15 months 2nd dose at school entrance (4-6 years) *infection confers lifelong immunity

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Respiratory Syncytial Virus

Introduction to Respiratory Syncytial Virus or RSV infection ..................................................32 Symptoms, Pathogenesis ...........................................................................................................33 Diagnosis, Prevention and Treatment .......................................................................................34

26

Introduction to Respiratory Syncytial Virus or RSV infection

-also called Pneumovirus -infects the respiratory tract -forms multinucleate cells mode of transmission: through aerosols or droplet sprays -peak incidence: winter and early spring -individuals susceptible to serious disease -children under 6 months or younger -5 in 1,000 newborns are affected -most prevelent cause of respiratory infection in newborns -mortality -highest in children with complications -premature -with congenital diseases -with immunodeciency

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Symptoms, Pathogenesis
-portals of entry: epithelia of the nose and eyes -main site of RSV replication: nasopharynx -primary infection -rst symptoms -fever that lasts 3 days -rhinitis -pharyngitis -otitis -infections of the bronchial tree and lung parenchyma -croup -bouts of coughing -wheezing -dyspnea -abnormal breath sound -adults and older children -manifest as a common cold -cough -nasal congestion -sometimes asymptomatic

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Diagnosis, Prevention and Treatment

Diagnosis is more important in babies than in older children or adults -conspicuously ill -signs and symptoms of pneumonia and bronchitis Diagnostic procedures that demonstrate the viral antigen directly from specimens a. direct or indirect uorescent staining b. ELISA c. DNA probes Treatment 1. administration of RSV immunoglobulin -highly benecial new treatment -serum is obtained from people with high RSV antibody titer -greatly reduces the complications -reduces the need for hospitalizations 2. Ribavirin -an antiviral drug -given as an inhaled aerosol 3. supportive measures -antipyretics to reduce fever -assist pulmonary ventilation -treat secondary bacterial infection

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Rhabdoviridae
Rabies virus
Introduction ...............................................................................................................................37 Epidemiology of Rabies ...........................................................................................................38 Infection and Disease ...............................................................................................................39 Clinical Phases of Rabies ........................................................................................................40 Diagnosis of Rabies ..................................................................................................................41 Rabies Management, Prevention and Control ........................................................................42

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Rabies virus
Introduction .................................................................................................................................37 Epidemiology of Rabies ..............................................................................................................38 Infection and Disease .................................................................................................................39 Clinical Phases of Rabies ...........................................................................................................40 Diagnosis of Rabies ....................................................................................................................41 Rabies Management, Prevention and Control ...........................................................................42

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Introduction
Rabies virus -most conspicuous rhabdovirus -belongs to the genus Lyssavirus -origin of the word -Rhabdovirus: Greek word "rhabos" -rod -refers to its bullet or bacillary form -rabies: Latin word "rabidus" -rage or fury Structure: -distinctive bullet-like appearance -round on one end, at on the other end -helical nucleocapsid -glycoprotein spikes that protrude through the envelope Rhabdovirus family -approximately 60 different viruses -only rabies lyssavirus infects humans -origin of the word: -lyssavirus: Greek word "lyssa" -madness

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Epidemiology of Rabies
-a slow, progressive zoonotic disease -characterized by a fatal meningoencephalitis -distributed worldwide except in developed countries -have remained rabies-free by practicing strict animal control -primary wild reservoirs -wild animals: canines, skunks, raccoons,badgers, cats and bats -they can spread the infection to domestic dogs and cats -both wild and domestic mammals can spread the disease to humans -through bites -scratches -inhalation of droplets Annual worldwide total for human rabies: estimated at 30,000 cases

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Infection and Disease

Infection begins when the infected animal's saliva enters a puncture site -occasionally the virus is inhaled virus is inoculated orally Rabies virus -remains up to 1 week at the trauma site -multiplication occurs -gradually enters the nerve endings -advances towards the ganglia, spinal cord and brain -viral multiplication throughout the brain -migration to other sites -eyes, heart, skin and oral cavity -completion of the infection cycle -when the virus replicates in the salivary glands -shed in the saliva

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Clinical Phases of Rabies

average incubation period -1 to 2 months or more length of incubation period depends on the following factors 1. wound site 2. severity of the bite 3. inoculation dose Shorter incubation period -in facial, scalp or neck wounds: greater proximity to the brain Prodromal phase -fever, nausea, vomiting, headache, fatigue and other nonspecic symptoms -pain, burning, prickling or tingling sensations at the wound site Second phase (2 forms of rabies) 1. Furious form of rabies -rst acute signs of neurological involvement -periods of agitation -disorientation -seizures -twitching -spasms in the neck and pharyngeal muscles -leads to severe pain on swallowing -sight of liquids bring on hydrophobia (fear of water) -the patient is fully coherent and alert 2. Dumb form of rabies -patient is not hyperactive -paralyzed, disoriented and stuporous Coma phase -death from cardiac or respiratory arrest can occur -humans were never known to survive rabies -as of 2002, there were 3 patients who have recovered from rabies

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Diagnosis of Rabies
Diagnosis can be made: -when typical symptoms appear after a rabid animal attack Diagnosis can be delayed: -when contact with the infected animal is not clearly dened -when symptoms are absent or delayed Can be misdiagnosed as -psychoneurosis: anxiety, agitation and depression -tetanus: muscle spasm -other viral infections: encephalitis with convultions and paralysis Often diagnosed during autopsy. Criteria indicative of rabies -intracellular inclusions (Negri bodies) in nervous tissues -identication of the rabies virus in the saliva or brain tissue -demonstration of rabies virus antigens in specimens of the brain, serum, CSF, or cornea using immunouorescent methods

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Rabies Management, Prevention and Control

Steps to do after a bite from a wild or stray animal 1. assessment of the animal 2. meticulous care of the wound 3. specic treatment regimen A wild animal that bites without provocation is presumed to be rabid -therapy should be immediately started If the animal is captured, brain samples and other tissues should be examined for the verication of rabies. Healthy domestic animals are not killed. -quarantined -observed closely for signs of disease -preventive therapy is initiated if any signs of rabies appear Wound care -washed with soap or detergent and water immediately -debridement -application of antiseptic Treatment -Passive immunization -HRIG (human rabies immune globulin) -1/2 of the dose: inltrate the site of bite -to stop the spread of the virus -1/2 of the dose: inject intramuscularly to provide immediate systemic protection -Active immunization -vaccine of choice: HDCV (human diploid cell vaccine) -a potent inactivated vaccine -cultured in human embryonic broblasts -route: intramuscular -schedule for postexposure vaccination: D1, D3, D7, D14, D28, and D60 + 2 boosters High-risk groups: given 3 doses to protect against possible exposure -veterinarians -animal handlers -laboratory personnel -travellers Control measures: -vaccination of domestic animals -elimination of strays -strict quarantine practices

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Filoviridae
Introduction .................................................................................................................................44 Transmission of EBOV and MARV .............................................................................................45 Viral Structure and Composition ................................................................................................46 Clinical Features/Presentation ...................................................................................................47 Host Response ............................................................................................................................48 Treatment and Prevention ..........................................................................................................49

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Introduction
First lovirus outbreak -1967 -occured in Germany and Yoguslavia -among laboratory workers handling African green monkeys and/or tissues from contaminated monkeys imported from Uganda -the causative agent was identied as a new virus called Marburg virus (MARV) 1975 -MARV re-emerged in Johannesburg, South Africa -a man who recently returned from Zimbabwe became ill and eventually died 1976 -a mysterious outbreak swept through several remote villages in Africa -the disease was rapidly fatal -88% mortality -a previously unknown virus similar to MARV was implicated -named Ebola virus -after a local river in Central Africa -it was the 2nd member of the Filoviridae family The source of outbreaks remains undetermined. -no approved vaccine or therapeutic intervention 1989 -an outbreak in a colony of monkeys imported in the Philippines to a holding facility in Reston, Virginia -highly lethal in nonhuman primates -no disease was reported in any human exposures 1994 -the 4th species was identied as ICEBOV -infection was acquired by a researcher during a necropsy to determine the cause of death of local chimpanzee populations 1995 -largest outbreak of EBOV in Kikwit, Democratic Republic of Congo -a total of 310 cases with 250 deaths Family Filoviridae -2 genera a. Marburgvirus 1. Lake Victoria marburgvirus b. Ebolavirus -four distinct species 1. Zaire ebolavirus (~90% lethal) 2. Sudan ebolavirus (~50% lethal) 3. Reston ebolavirus (unknown lethality) 4. Ivory Coast ebolavirus (unknown lethality)

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Transmission of EBOV and MARV

by direct contact with the blood, secretions, organs, or other bodily uids from infected persons or animals particularly chimpanzees and gorillas Rapid spread and amplication is associated with -hospitals -virus is spread through nosocomial routes -burial ceremonies -mourners have direct contact with the deceased The modes of transmission has been well documented but the true source of the outbreaks has not been identied. -bats have been implicated as the reservoirs.

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Viral Structure and Composition

-enveloped, nonsegmented, negative strand RNA viruses -envelope is derived from the lipid membrane envelope from the host plasma membrane -thread-like, lamentous morphology -pleomorphic: can range from straight tube-like structures, branched structures to curved laments shaped like a 6, a U or a circle -diameter is typically 80nm -average length can vary from 800-1,000nm -MARV closer to 800nm -EBOV closer to 1000nm -virus has seven viral proteins a. surface projections of glycoproteins are dispersed evenly over the entire surface at 10nm intervals -for attachment -receptor-mediated endocytosis -fusion with endocytic vesicles -release of the virion core into the host cell cytoplasm -no specic host-cell receptor has been identied b. the remaining six proteins are found within the virion -VP 40: functions as a matrix protein essential for efcient viral assembly and budding -VP24: participates in the spontaneous formation of the nucleoprotein complex behaves like a minor protein matrix -NP (nucleoprotein), VP30, VP35, polymerase proteins (or L protein) and viral genomic RNA form the ribonucleoprotein complex -nucleocapsids: helical lamentous structure

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Clinical Features/Presentation
comparable with that of severe sepsis or septic shock incubation period: 2-21 days initial presentation -nonspecic symptoms -high fever, chills, malaise and myalgia multisystemic involvement -as the disease progresses -prostration, anorexia, vomiting, nausea, abdominal pain, diarrhea, shortness of breath, hypotension, edema, confusion, maculopapular rash, and eventually coma -rapid progression -death occurs in 6-9 days after the onset of symptoms indications of abnormalities in coagulation and brinolysis -development of petechia, echymosis, mucosal hemorrhages -uncontrolled bleeding at venipuncture sites massive blood loss is atypical -if present, it is restricted to the GIT fulminant infection evolves to shock, convulsions and diffuse coagulopathy

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Host Response
In fatal EBOV infection -dysregulated cytokine expression levels -coagulation abnormalities -brin deposition -DIC -evidence of cell death -lack of adaptive immune response Fatal cases are associated with the lack of B-cell or T-lymphocyte immune response

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Treatment and Prevention

No approved therapies or vaccines for the treatment and/or prevention of EBOV and MARV. Control and treatment are limited to containment and basic supportive measures. Treatment -uid and electrolyte replacement -pain reduction Control -isolation of infected patients -strict-barrier nursing techniques implemented -contact-tracing is important -proper disinfection and handling of clinical specimens -patient education -presentation of the disease -transmission -possible source

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Single-Stranded, Positive-Sense, Reverse Transcriptase

Retroviridae AIDS (HIV)
Introduction for Retroviridae .................................................................................................53 Biology of the Retroviruses ...................................................................................................54 Structure and Behavior of Retroviruses ...............................................................................55 Historical Background of AIDS ..............................................................................................56 Origin of AIDS .........................................................................................................................57 Epidemiology of AIDS ............................................................................................................58 Clinical Denition of AIDS .....................................................................................................59 Case Descriptions According to Group, in order of prevalence .........................................60 Modes of Transmission ..........................................................................................................62 Misconceptions: How AIDS is NOT Transmitted .................................................................63

AIDS Pathology
Initial Infection of Target Cells ............................................................................................65 Stages of HIV Infection and Disease ..................................................................................67 The Primary Effects: Harm to T-cells and the Brain .........................................................68 Secondary Effects That Dene AIDS ..................................................................................69 Effects of Co-infection .........................................................................................................71 Testing for HIV ........................................................................................................................72 AIDS Therapy ..........................................................................................................................73 AIDS Protection ......................................................................................................................75 Will There Be an AIDS Vaccine? ............................................................................................76

Other Retroviral Diseases in Humans

Adult T-cell Leukemia (ATL) ...................................................................................................78 Hairy-cell Leukemia (HCL) .....................................................................................................79

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Retroviridae
AIDS (HIV)
Introduction for Retroviridae ...................................................................................................53 Biology of the Retroviruses .....................................................................................................54 Structure and Behavior of Retroviruses .................................................................................55 Historical Background of AIDS ................................................................................................56 Origin of AIDS ...........................................................................................................................57 Epidemiology of AIDS ...............................................................................................................58 Clinical Denition of AIDS ........................................................................................................59 Case Descriptions According to Group, in order of prevalence ...........................................60 Modes of Transmission ............................................................................................................62 Misconceptions: How AIDS is NOT Transmitted ...................................................................63

AIDS Pathology
Initial Infection of Target Cells ...............................................................................................65 Stages of HIV Infection and Disease .....................................................................................67 The Primary Effects: Harm to T-cells and the Brain ............................................................68 Secondary Effects That Dene AIDS ....................................................................................69 Effects of Co-infection ...........................................................................................................71 Testing for HIV ...........................................................................................................................72 AIDS Therapy ............................................................................................................................73 AIDS Protection ........................................................................................................................75 Will There Be an AIDS Vaccine? ..............................................................................................76

Other Retroviral Diseases in Humans

Adult T-cell Leukemia (ATL) .....................................................................................................78 Hairy-cell Leukemia (HCL) .......................................................................................................79

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AIDS (HIV)
Introduction for Retroviridae ......................................................................................................53 Biology of the Retroviruses ........................................................................................................54 Structure and Behavior of Retroviruses ....................................................................................55 Historical Background of AIDS ..................................................................................................56 Origin of AIDS ..............................................................................................................................57 Epidemiology of AIDS .................................................................................................................58 Clinical Denition of AIDS ..........................................................................................................59 Case Descriptions According to Group, in order of prevalence ..............................................60 Modes of Transmission ...............................................................................................................62 Misconceptions: How AIDS is NOT Transmitted ......................................................................63

AIDS Pathology
Initial Infection of Target Cells .................................................................................................65 Stages of HIV Infection and Disease .......................................................................................67 The Primary Effects: Harm to T-cells and the Brain ..............................................................68 Secondary Effects That Dene AIDS .......................................................................................69 Effects of Co-infection ..............................................................................................................71 Testing for HIV .............................................................................................................................72 AIDS Therapy ...............................................................................................................................73 AIDS Protection ...........................................................................................................................75 Will There Be an AIDS Vaccine? .................................................................................................76

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Introduction for Retroviridae

among the most unusual viruses -they have known oncogenic abilities -they cause fatal disease -they are capable of altering a host's DNA most common are the lentiviruses where HIV or Human Immunodeciency Virus belongs -causes AIDS or Acquired Immunodeciency Syndrome

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Biology of the Retroviruses

-they are equipped with an enzyme called reverse transcriptase -catalyzes the replication of dsDNA from ssDNA -they reverse the order of transcription --> retroviruses -viral genes are permanently integrated into the host's genome as a provirus -passed on to progeny cells -transform cells -regulate certain host genes -they convert normal cells into cancer cells Nomenclature and Classication A. lentivirus group -the rst human retroviruses isolated 1. HTLV I & II -human T-cell lymphotrophic viruses I & II -associated with human leukemia or lymphoma 2. HTLV III -given the name HIV -there are 2 types a. HIV-1: the dominant form in most of the world b. HIV-2: exists primarily in western Africa

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Structure and Behavior of Retroviruses

Display structural features typical of enveloped RNA viruses. -lipid envelope: the outermost component -2 glycoprotein spikes and knobs -mediate adsorption to the host cell a. GP-120 b. GP-41 -encased inside a protein coating -2 identical RNA strands -several molecules of reverse transcriptase -most retroviruses can infect only host cells that present the required receptors. -in the case of AIDS virus, the target cells possess a. CD4 receptors b. a coreceptor called CCR-5 (fusin) -these receptors -permit docking with the host cell -allow fusion with the cell membrane of leukocytes and tissue cells

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Historical Background of AIDS

First cases of AIDS were seen by physicians in LA in San Francisco in New York City -clusters of young male patients with one or more of a complex of symptoms: -severe pneumonia caused by P. carinii (usually a harmles fungus) - a rare vascular cancer called Kaposi sarcoma -sudden weight loss -swollen lymph nodes -general loss of immune function -all these young men were homosexuals -early hypothesis to explain the disease -a consequence of the homosexual lifestyle -a result of immune suppression by chronic drug abuse -a result of immune suppression by infection -these cases however were soon reported in -nonhomosexual patients transfused with blood or blood products -eventually, virologists from the Pasteur Institute in France were able to isolate a retrovirus -the disease was clearly communicable -it was termed by the medical community as AIDS

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Origin of AIDS
HIV-1 and HIV-2 are not closely related to each other HIV-1 and HIV-2 are both closely related to SIV. -HIV-1 shares a heritage with SIV (a virus of chimpanzees) -HIV-2 shares a heritage with SIV (a virus from sooty Mangabey monkeys) The 2 HIVs originate from separate evolutionary events
CPZ SM

First well-documented case of AIDS -1959 -in an African man -his blood sample yielded genetic material from an early version of HIV HIV probably remained in small isolated villages. -it causes only sporadic cases -it mutated into more virulent strains Factors that cause rapid spread -changing social and sexual norms -increased immigration and travel

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Epidemiology of AIDS
Statistic patterns -reported in every country -estimates of currently infected -35 to 40 million worldwide -approx 1 million in the US -majority have not begun to show symptoms -in the latent phase of the disease AIDS (US data) -became a notiable disease at the national level: 1984 -has continued in an epidemic pattern -gradually decreased since 1994 -50% mortality -more common among males than females

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Clinical Denition of AIDS

Denition: -a severe immunodeciency arising from infection with HIV -accompanied by some of the following symptoms -life-threatening opportunistic infections -persistent fever -unusual cancers -chronically swollen lymph nodes -extensive weight loss -chronic diarrhea -neurological disorders At some point in the infection, the patient tests (+) for antibodies to HIV -it means that an infection with HIV has taken place -it does not indicate that the disease exist -it is presumed that the person is infectious CDC standard system for staging HIV infection and AIDS -places an HIV-infected person into a particular clinical category based on -the state of his immune system -the degree and type of symptoms

PGL-persistent generalized lymphadenopathy AIDS-indicator conditions -opportunistic infections -cancers, wasting, dementia Overt AIDS -belonging to C1, C2, C3, B2 and B3

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Case Descriptions According to Group, in order of prevalence

the following categories summarizes the primary exposure and risk categories for HIV infection and AIDS I. Homosexual or Bisexual Males -male homosexuals accounts for the majority of AIDS cases (45%) -increased susceptibility due to anal sex -lacerates the rectal mucosa -provides an entrance for viruses from semen to blood -the passive anal partners are more likely to become infected -bisexual males infects the females and the general heterosexual population -rate of infection in this group appears to be declining II. Intravenous Drug Users -in large metropolitan areas like New York City, 60% of IV drug addicts can be HIV carriers -especially pronounced when needles are shared -this group is growing more rapidly than any other mode of transmission -another signicant factor in the spread of AIDS to the heterosexual population -some cities hand out sterile needles or disinfection kits to drug users III. Heterosexual Sex Partners of HIV Carriers -in most parts of the world, heterosexual intercourse is the primary mode of transmission -in the US, 12% of AIDS cases arise from unprotected sexual intercourse with an AIDSinfected partner of the opposite sex -drug addicts -bisexual men -prostitutes -spouses of people who have received transfusions -multiple sexual encounters increases the chance of infection -every single encounter is known to transmit the virus -rate of heterosexual infection has increased dramatically in the past years in adolescent and young adult women. -currently, 1/3 of new cases occur in women IV. Blood Transfusion and Blood Products -no longer a serious risk because of blood donor screening -there can be a lag period of a few weeks to several months before antibodies appear in the infected person -if screening is done during the lag period, antibodies are not detected -rarely, organ transplants can carry HIV: should also be tested -other blood products were once implicated (serum, coagulation factors) -1980s and 1990s -thousands of hemophiliacs died from the disease V. Inapparent or Unknown Risk Factors -6% of cases can occur in people with no apparent risk factors -but with careful study of their history -have a prior contact with a prostitute -have a history of other STDs -factors that make it impossible to explain the case

-have a prior contact with a prostitute -have a history of other STDs -factors that make it impossible to explain the case -patient denial -unavailability -death -uncooperativeness VI. Congenital or Neonatal AIDS -majority of mothers are -young IV drug addicts -sex partners of drug addicts -chance of an HIV+ mother infecting her fetus: 1 in 3 -infected babies develop the disease more rapidly than adults -prevention of fetal infection -treatment of infected mothers with a combination of anti-AIDS drugs VII. Risks Involving Medical and Dental Personnel -Chances of getting the infection with a needlestick accident -1 in 500 -transmission of HIV will not occur through casual contact or routine nursing procedure.

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Modes of Transmission
2 forms of contact a. sexual intercourse b. transfer of blood or blood products Virus -does not survive long outside the host -sensitive to heat and disinfectants Infection can take place -if the virus crosses the body's epithelial barriers into the uid compartments HIV-infected people -harbors high levels of free virus and infected leukocytes -semen and vaginal secretions also harbor free virus and infected WBC -lactating mothers: milk contains signicant numbers of leukocytes Body uids wherein the virus can be isolated in small numbers: -urine, tears, sweat and saliva

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Misconceptions: How AIDS is NOT Transmitted

-inhaling droplets -shaking hands -handling fomites -sharing public facilities, food and swimming pools -transmission by blood-sucking insects -not biological vectors of AIDS -do not harbor the virus in infectious doses Inaccurate notions and misconceptions have added to the fear of AIDS and should be corrected.

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AIDS Pathology
Initial Infection of Target Cells ....................................................................................................65 Stages of HIV Infection and Disease ..........................................................................................67 The Primary Effects: Harm to T-cells and the Brain ................................................................68 Secondary Effects That Dene AIDS .........................................................................................69 Effects of Co-infection ................................................................................................................71

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Initial Infection of Target Cells

HIV enters mucous membranes or the skin -injection -trauma -direct passage It travels to dendritic cells. -found beneath the skin -it grows inside -it shed by the cell without being killed Amplication -multiply in the macrophages in skin, lymph nodes, bone marrow, and blood It infects and destroys cells that are supposed to kill the virus. -helper class of lymphocytes -monocytes -macrophages -B lymphocytes Virus docks onto host cell receptors -CD4 -CCR-5 Once inside the cell -its reverse transcriptase makes DNA out of the RNA genome It enters a latent period in the nucleus of the host cell. -reason for the lengthy course of the disease -the viral DNA becomes integrated into the nucleus

After a latent period -various immune activators stimulate the infected cell -reactivation of provirus genes -production of viral mRNA

HIV mRNA is translated by the cells synthetic machinery into virus components -capsid -reverse transcriptase

HIV mRNA is translated by the cells synthetic machinery into virus components -capsid -reverse transcriptase -spikes Viruses are assembled. Budding of mature viruses lyses the infected cell.

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Stages of HIV Infection and Disease

Initial infection -vague symptoms that soon disappear Period of asymptomatic HIV infection -incubation period varies: 2-15 years (ave 10yrs) First antibodies to HIV -detected in the serum by the 2nd month following infection -ineffective in neutralizing the virus once it enters into the latent phase Initial presentation -fever -swollen lymph glands (persistent LAD) -fatigue -diarrhea -weight loss -neurological symptoms -opportunistic infections -neoplasms Not everyone who becomes infected or is antibody (+) develop AIDS. -5% of infected people remain free of disease -these people who remain healthy are termed as "nonprogressors" -lack the receptors that HIV requires -infected by a weakened virus mutant

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The Primary Effects: Harm to T-cells and the Brain

During the long period of chronic infection -the infected cells play host to the virus either in the latent phase or in the active phase Cells with active viruses -T-cells and other white blood cells -release large quantities of the virus into the circulation -killed in the process -extreme leukopenia -loss of essential T4 memory clones and stem cells The virus -will cause the formation of giant T-cell and other syncytial cells -would allow the spread of virus directly from cell to cell -mass destruction of the syncytial cells afterwards As the number of viruses in the circulation increases, the cycle continues -greater infection rate -greater death of cells -greater viral burden The T4 lymphocytes have multiple cytotoxic, helper and inducer functions. -their destruction paves the way for invasion by opportunistic agents and cancer When T4 cell levels fall below 200cells/cumm, symptoms of AIDS appear. Target of the AIDS virus -immune system -central nervous system Infected macrophages cross the blood-brain barrier and release viruses. -invade nervous tissue -viral envelope protein have a direct toxic effect on the glial and other cells in the brain -peripheral nerves become demyelinated -brain becomes inamed

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Secondary Effects That Dene AIDS

Opportunistic infections -are among the earliest symptoms of AIDS -debilitating and potentially fatal -involve fungi, protozoa, viruses or bacteria -they establish a foothold in the absence of adequate cytotoxic immunity -most frequent sites of attack -respiratory -digestive -nervous system Fungal infections a. Pneumocystis carinii pneumonia -leading cause of mortality and morbidity in AIDS patients -fever, cough, shortness of breath -thickening of the lung epithelium -uid inltration of the lungs b. Cryptococcus neoformans -causes meningitis c. Candida albicans -attack the oral, pharyngeal and esophageal mucosa d. Aspergillus spp. -infects the lungs Protozoan infection a. Toxoplasma gondii -toxoplamosis of the brain b. Cryptosporidium -diarrhea Viruses a. Herpes simplex and herpes zoster -can reactivate -produce severe ulceration of the skin, lips, genitalia and anus b. Cytomegalovirus -disseminated pneumonia -can infect the brain, eyes and liver Bacteria a. Mycobacterium tuberculosis -TB in AIDS patients are now at epidemic level b. Mycobacterium avium complex -grow in massive number in the bone marrow, liver, spleen and lymph nodes AIDS-associated Cancers -due to the loss of the natural cancer-killing T-cells -intrusion of organisms that can cause cancer a. Kaposi sarcoma -cancer that is most seen clinically -caused by herpesvirus -a nodular purple lesion that develops from endothelial cells in blood vessels of the

-cancer that is most seen clinically -caused by herpesvirus -a nodular purple lesion that develops from endothelial cells in blood vessels of the skin, intestine and mucuos membrane -other effects: lymphadenopathy, weight loss, hemorrhage, perforation and intestinal obstruction

b. epithelial carcinomas -skin, mouth and rectum c. lymphomas -originating from B lymphocytes Miscellaneous conditions -nonspecic, disease-related symptoms -appear to involve severe immune deregulation, hormone imbalances and metabolic disturbances -weight loss, diarrhea and poor nutrient absorption: pronounced wasting of body mass -protracted fever, fatigue, sore throat and night sweats: signicant & debilitating -patients with nervous system involvement -withdrawal -persistent memory loss -spasticity -sensory loss -progressive AIDS dementia -rashes and generalized lymphadenopathy -presenting signs in many AIDS patients

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Effects of Co-infection
-effect of coinfection with STDs -genital ulcers present in chlamydia, syphillis and warts -breaks in the mucous membrane provide both a route of exit and entry for the virus -coinfection with Epstein-Barr virus, cytomegalovirus, TB, hepatitis B and mycoplasma -the severe immune suppression accompanying AIDS enhances the pathogenecity and virulence of these infections

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Testing for HIV

basis: detection of antibodies specic to the virus in serum and other uids -this would allows for the rapid, inexpensive screening of a large number of samples -testing would proceed at 2 levels 1. initial screening a. ELISA: an older method b. latex agglutination c. oral swab tests -these tests are accurate but 1% may give falsepositive results and require a follow-up more specic test 2. conrmatory test a. Westerm blot analysis -detects several different anti-HIV antibodies -can rule out a false-positive result False-negative results -can occur in 1/4 patients -due to silent infections -variation in the onset of antibody production -to rule out false-negative results -do a second test later b. direct discovery of HIV, its genes, or antigens in blood and other specimens -can eliminate false-negative results that are inherent in antibody analysis -good in monitoring blood for transfusion Western blot analysis -tests for antibodies to specic HIV antigens -prepared by electrophoresing several of the major HIV surface and core antigens -these are blotted them onto special lters -test strips are incubated with a patients serum and developed with a radioactive or colorimetric label -sites where HIV antigens have bound antibodies show up as bands

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AIDS Therapy
No cure for AIDS Purpose of therapy -focus on supportive care -drugs given to control opportunistic and HIV infections Drugs to control PCP -Cotrimoxazole -Pentamidine For cytomegalovirus -ganciclover and foscarnet Disseminated fungal infections -uconazole Kaposi sarcoma -responds to alpha interferon and human chorionic gonadotropin Drugs to inhibit infection and replication by the AIDS virus. a. synthetic nucleoside analog -reverse transcriptase inhibitors -azidothymidine (AZT) -didanosine (ddI) -epivir (3TC) -stavudine (d4T) -inserted in place of the natural nucleoside by reverse transcriptase -they interrupt HIV multiplication by mimicking the structure of actual nucleosides -these drugs lack all the correct binding sites for further DNA synthesis -viral replication and the viral cycle are terminated b. other reverse transcriptase inhibitors that are not nucleosides -nevirapine and sustiva -bind to the enzyme and restructures the enzyme c. protease inhibitors -crixivan, norvir, and agenerase -block the action of HIV enzyme involved in the nal assembly and maturation of the virus -plug into the active sites on HIV protease -HIV protease is necessary to cut elongate HIV protein strands and produce functioning smaller protein units -the enzyme is blocked -the proteins remain uncut and abnormal defective viruses are formed

-the proteins remain uncut and abnormal defective viruses are formed HAART regimen -most effective in controlling AIDS and drug resistance -highly active anti-retroviral therapy -combine two reverse transcriptase inhibitors and one protease inhibitor in a cocktail -the virus is interrupted in two phases of its cycle -successful -in reducing viral load to undetectable levels -in facilitating the improvement of the immune function -in reducing the rate of virus drug resistance -in reducing the incidence of AIDS death -patients who are HIV (+) but asymptomatic can remain healthy with this therapy -drawbacks: -high cost -toxic side effects -drug failure due to patient noncompliance -unable to completely eradicate the virus c. integrase inhibitors -a new class of experimental drugs -attach to the enzyme required to splice the dsDNA of HIV into the host genome -act at the stage of viral integration into the host DNA molecule -prevent formation of the provirus and block future virus multiplication in that cell d. other drugs under experiment and consideration 1. fusion inhibitors: prevent attachment of HIV to the host cell 2. ribozymes: inhibit translation of the viral RNA 3. interferon: prevents virus replication

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AIDS Protection
-follow a monogamous lifestyle -screen prospective sex partners -use "safe-sex" practices -use of condoms with an antimicrobic spermicide -avoidance of anal sex -not sharing syringes and needles -disinfecting the syringe and needle with hypochlorite solution before use

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Will There Be an AIDS Vaccine?

"Trojan horse" or Viral vector technique -a way of making AIDS vaccine -the part of the HIV genome coding for envelope glycoproteins is inserted into the carrier virus. -this hybrid virus replicates and expresses the HIV genes when it is injected into a host. -more than 70 vaccines in various stages of development and testing -no workable vaccine available yet

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Other Retroviral Diseases in Humans

Adult T-cell Leukemia (ATL) .......................................................................................................78 Hairy-cell Leukemia (HCL) ..........................................................................................................79

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Adult T-cell Leukemia (ATL)

-rst described by physicians working with a cluster of patients in southern Japan - a similar disease was later described in Caribbean immigrants -it was found out that these diseases and a cancer called Sezary-cell leukemia were the same -linked to HTLV-1 (human lymphotrophic virus-1) -the disease is not highly transmissible -repeated close or intimate contact is required -virus is transferred in infected blood cells -blood transfusion and blood products are potential agents of transmission -IV drug users could spread the virus -a chronic disease, invariably fatal in its course -symptoms: -extreme, persistent lymphocytosis with large atypical lymphocytes Mycosis fungoides or Cutaneous T-cell Lymphoma -one variant of ATL -accompanied by dermatitis with thickened, scaly ulcerative or tumurous skin lesions -other complications -lymphadenopathy -dissemination of the tumors to the lung, spleen and liver Treatment -drugs, radiation and combinations of both have been tried -long-term prognosis remains poor

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Hairy-cell Leukemia (HCL)

-rare form of cancer that has been traced to HTLV-II infection -derives its name from the appearance of the aficted lymphocytes -ne cytoplasmic projections or pseudopod-like extensions -more common in males than females -spread through blood and shared needles and syringes -presentation -presents with overall leukopenia -with an increased number of neoplastic B lymphocytes -most serious complication -inltration of the spleen, liver and bone marrow -treatment options pursued -splenectomy -bone marrow transplants -antineoplastic drugs -alpha-interferon produces the highest rate of remission -