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02. .15
Introduction
Poliomyelitis one of the earliest evidences
- Egyptian priest
- From hieroglyph
Rabies also led to the discovery of the virus when it could not be explained by the presence of bacteria.
1940s Electron Microscopy- start of study (chemical nature of virus)
- infectivity mainly studied in animal models
Viral Capsid
protect the viral nucleic acid from detrimental physical and chemical conditions.
Chapter 5: VIRUS
02. .15
Viral Envelope-
Viral Receptors-
Chapter 5: VIRUS
02. .15
Asymptomatic Viral Infections- virus replicates w/in the host but doesnt produce symptoms of a disease
HIV-
H IV co re
p e ne tra te s
ce ll cy to p la sm
U nc o a tin g ,
re le a se o f 2
RNA &
re v e rse
tran scrip tas
e in to
cy top la sm
Re v e rse
tra nscrip ta se
co p ie s R N A
itno ss D N A
ss D N A
du plica te d to
fo rm ds D N A
(cop y of th e
o rigin a l v ira l R N A
ge n o m e )
D N A m o ve s
in to h o st ce ll
n ucle u s
DNA
in te g ra te d a s
P R O V IR U S
in to a h ost
c ell
ch ro m o so m e
the provirus may lie dormant or can produce viral mRNA (polycistronic) & proteins to resume the
multiplication cycle producing virions
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10
progression of the disease by restoring & maintaining the number of T4 helper lymphocytes.
Tumour Virus
-
virus infected cells change dramatically, acquiring the characteristic of tumour cells exhibiting
uncontrolled growth.
Acquisition of viral genes by the host must be followed by other events as environmental or dietary
exposures to chemical carcinogen for cancer to occur
Chapter 5: VIRUS
02. .15
Direct Injection- only the naked DNA will enter the host cell
Fusion- viral envelope will bind with host cell membrane, liberating the viral capsid w/in the
cell cytoplasm
- Endocytosis- the whole virus will be engulfed by the host cell, forming a Cystolic Vacuole.
3. Uncoating of the viral particle
- Viral nucleic acid needs to be released from the capsid
- Penetration by Endocytosis: acidification of cystolic vacuole induces a conformational change in
the capsid & the release of viral nucelocapsid into the cytoplasm
- Some like Reovirus only needs a partial uncoatingfor the expression of the viral genome
4. Replication of viral nucleic acids & translation of the genome
- the host cell synthesis is taken over by the virus
transcription of viral genes into viral
mRNA
Chapter 5: VIRUS
02. .15
In principle, cell culture for propagating viruses replies on the growth of cells in a Semiconfluent
Monolayer attached to a surface
To subculture, the cells are separated from the monolayer w/ the use of Trypsin to form a suspension of
37 C
Control of Virus
Antiviral Chemotherapy- most are pro drugs that need to be activated within the cell (by Kinase & Other
cellular
enzymes)
- Role: slow or halt disease progression. Not cure.
- target Viral enzymes: Protease; Polymerases; Reverse Transcriptase
- Protease- particularly important for uncoating process preventing the release of viral
nucleocapsids
- Neuraminidase Inhibitors- prevents the release of mature virions
HIV
Antiretrovirals- antiviral drugs
- Aim to reduce HIV plasma levels for as much and as long as possible
- Side effects:
Immune Recinstitution syndrome
Cough
Headache
Lipodystrophy syndrome- includes:
Insomnia
fat redistribution insulin resistance;
Dizziness
hyperglycaemia; dyslipidaemia
Fatigue
Liver damage
Blood disorder
Osteonecrosis
Myalgia
GI Disturbance
Arthralgia
Anorexia
Rash
Pancreatitis
Urticaria
Dyspnoea
fever
-
Protease Inhibitors- metabolized by Cytochrome P-450 & therefore have significant potential for
drug
Interaction
Non-nucleoside Reverse Transcriptase Inhibitor- interact with a number of drugs metabolized in
the liver
Side effects:
Rash
Chapter 5: VIRUS
Psychiatric disturbance
CNS disturbance
Fatal hepatitis
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Herpesvirus Infection
Systemic antivirals- given within 24 hrs onset of rashes, for adults infected w/
chickenpox
- Given within 27hrs onset of rashes, for adults infected w/ shingles
Side effects of Herpes Antivirals:
Nausea
Fatigue
Vomiting
Rash
Stomach pain
Increase in serum
Headache
Increase in urine uric acid
Influenza
Oseltamivir- Antiviral that was recommended for txt of influenza by National Institute & Clinical
Excellence (NICE)
- extensively used for prevention and control of the swine flu outbreak in UK 2009
- LIMITATIONS: Drug needs to be taken w/in a few hours of the onset of symptoms
Txt: Palivizumab (monoclonal antibody) & Ribavirin (antiviral drug), both associated with
side effects
Vaccination-
Contains antigens that elicit a specific and active immunity against an infecting agent
Can induce the innate and adaptive (cellular, humoral) parts of the immune system
Hepatitis B virus vaccine- recombinant vaccine where the viral DNA encoding for a virus surface
antigen (HBsAg) is
Chapter 5: VIRUS
02. .15
Human Papillomavirus (HPV)- contains virus-like particles & recombinant capsid protein expressed
in yeast or using a
Adjuvants in vaccines:
Aluminum Salts- antigens are absorbed to the aluminum salts
Monophosphoryl lipid A- increase or modulate host immunes response to the antigen
Human normal immunoglobulin (HNIG)- prepared from a pool of donated human plasma and
contains immunoglobulin G (igG) and antibodies against viruses like:
Hepa A
Rubella
Measles
Varicella
Mumps
Viruses are generally transmitted via surfaces & therefore the use of viricidal disinfectants on hard
surfaces & viricidal antiseptics on skin is important
Susceptibility to viricidal agents:
a. Small non-enveloped viruses are more resistant than large enveloped viruses
b. Lipid-rich envelope being damaged easily by chemical & physical agents, large enveloped
virus
Biocidal activity depends upon a number of factors, such as:
a. Concentration
b. Contact time
c. Presence of soiling
d. Formulation
Target site for biocide:
a. Envelope
b. Glycoprotein
c. Capsid
d. Viral nucleic acid
Highly reactive biocide that damages the capsid:
a. Aldehyde ex. Gulataldehyd
b. Oxidizing agents- ex. Peracetic acid, Hydrogen peroxide
H 2 O2 & Chlorine dioxide have been shown to penetrate within the capsid and
damage viral nucleic acid
Lesser reactive biocide that can only damage the capsid to a certain extent:
a. Quaternary ammonium compounds (QACs)
b. Biguanides- ex. Chlorhexidine
Viruses with a HELICAL CAPSID STRUCTURE are more susceptible since the destruction/alteration of
capsid is more likely to cause damage to the viral nucleic acid w/c is closely associated to this type of
structures
More viruses are susceptible to exposure to temperatures above 60 for 30 minutes
- used for inactivation of viral contaminants (HIV) in blood products
Viruses survive well at low temperatures and they can be routinely stored at -40 to -70
d. manufacturing process
e. capacity to remove/destroy and contaminate
A risk assessment/stringent control are applied to samples containing a component from human or
animal origin
For preparation of viruses, the inactivation process must ensure that it does not affect antigenicity
while killing the virus and other potential contaminants such as mycoplasmas
Prep of Influenza Vaccine, the inactivation process must cause minimum alteration of the
HAEMAGGLUTININ & NEURAMINIDASE antigens
certain viruses are used as vectors for the delivery of genes to targeted cells
Viruses used for Gene Transfer Medicinal Products:
a. (AAV) Adenoviruses
b. poxviruses
c. retroviruses
d. lentiviruses
e. adeno-associated viruses
f. herpesviruses
Viral vectors- for human use are freeze-dried/liquid prep of recombinant viruses, genetically modified
to transfer
rendered replication-incompetent.
Adeno-associated virus vectors- deficient adenovirus in which certain genes necessary for viral
replication have been replaced
Viruses as Antimicrobial
Phage typing- method that differentiates distinct strains of the same bacterial species on the basis of
their susceptibility to phages
Prions- can be recovered from the brains of infected individuals as rod-like structures which are
oligomers of a 30kDa glycoprotein
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