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7/30/2019 Retroviruses - 2013 (FN) [Compatibility Mode]
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Retroviruses, oncoviruses
and prions
Dr Faseeha Noordeen
Department of Microbiology
Faculty of MedicineUniversity of Peradeniya
May 2013
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Transmission and the pathogenesis of HIV / AIDS
The outcome of HIV / AIDS
Principles of diagnosis, management & prevention
of HIV / AIDS
Learning outcomes
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Aim: make students aware pathogenesis& clinical significance of retro,
oncogenic viruses and prions
Objectives:
1. to conceptualise the pathogenesis of retrovirus infections to diagnose these
(History + Symptoms + Lab)
2. to prevent/control in retro virus infectionsand prion disease
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RetrovirusesClassification: Disease, tissue tropism
and genomic identity
1. Oncovirus - HTLV 1, HTLV 2 and HTLV 5
2. Lentivirus - HIV 1 and HIV 2
3. Human foamy virus - Clinical importance?
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General features of retroviruses
First identified tumour virus
Medium sized and enveloped
Envelope GP
- Fusion protein - gp 41
- Attachment protein - gp 120
Virion
- 2 copies of RNA genome
- Reverse transcriptase and integrase
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HIV schematic diagram
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Genome - gag, pol and env genes
capsid enzymes envelope
Oncogenic retroviruses- Growth stimulating genes
- Captured cellular genes
- Resemble cellular genes
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HIV - Modes of transmission
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Retrovirus pathogenesis
1. Attachment
2. Entry3. Integration
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HIV attachment + fusion -
Molecular mechanisms
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Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings
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Attachment
Virus attaches to cell
specific receptorsHIV gp 120 to CD26 of
T lymphocytes
EntryEnvelope fuses with
cell membrane
RT synthesizes
complementary DNA
strand (cDNA)
Integration
cDNA integrated into
host DNA (Integrase)HIV RT causes mutations
(error prone)
Integrated cDNA istranscribed as a cellular
gene by host RNA
polymerase
Accessory proteins ofHIV regulate replication
and pathogenesis
Virus buds - envelope
Virus form syncytia - lysis
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Pathogenesis cont . Tropism - CD4 T cells & macrophages, neurons
HIV - lytic infections - T cells
- latent ,, - T cells & macrophages
- persistent ,, - T cells & macrophages
Continuous killing of (mature + stem ) T cells
Reduced T cells + Immunodeficiency
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Pathogenesis cont .Persistently infected M - reservoir +
distribution vehicle
HIV infection in neurones + brain M
Neurologic abnormalities
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Human Immunodeficiency Virus
(HIV)
(Depicted in green, budding offinfected white blood cell)
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Pathogenesis cont.
HIV infection
AIDS
Months to years
ARC Full blown
AIDS
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Laboratory diagnosis of HIV
infection
1. Serology - ELISA and latex agglutination
Confirmation - Western blot
2. Ag detection - HIVp 24 antigen - early
marker and indicator for active virus replication
3. Demonstration of viral NA - PCR and may be
useful because of its extremely high sensitivity
4. Prognostic test/CD4/CD8 ratio - A decreasein the ratio correlates with progression to AIDS
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Treatment
Resolution is prevented by the ability
of the HIV to
Inactivate immune system
Replicate in privileged sites
Alter its antigenicity
Drugs target RT and proteases
Epidemiology and prevention
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HTLV I and HTLV II
Acquisition - Venereal, blood transfusion
and breast feeding
Infection - CD4 T cells, remain latent and
replicate slowly for years
Transactivation - Viral tax proteins triggercellular genes & promote growth
Leukaemia - Chromosomal aberrations &rearrangements leukaemia
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Disease
Incubation period is > 30 years
Asymptomatic infections
Neoplasia of CD 4 T cells , elevated WCC
Can progress to adult acute T cell
lymphocytic leukaemia (ATLL)
Acute disease is fatal Also causes tropical spastic paraparesis
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Other Human oncogenes/viruses
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Prions
Infective particles, no genome and
structure
Aggregates of protease resistant GP
Do not elicit immune response
Resistant to inactivation
Infected brains have PrPsc infectious
PrPsc is similar to PrPc
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PathogenesisNo CPE in vitro studies
Long incubation period
Cause vacuolation + gliosis (spongiformchanges)
No inflammation and immune changes
Human disease - CJD and kuruAnimal disease - BSE - transmissible to
lab animals and man
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Which of the following
about HIV are true
1. HIV establishes lytic, persistent and latent
infections of CD4 T cells & also infects
macrophges & neurons2. HIV Infection in CD4 T cells does not induce
cytolytic syncytia
3. Mutation of HIV within an individual promotes
escape from immune control4. HIV p24 is an indicator of virus replication
5. Major anti HIV drug target is polgene product
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I . Name three infections
that can be transmittedduring this process
II . State how would youprevent these
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1. Write short notes on1.1. Prions and associated diseases
(50 marks)
1.2. Oncogenic viruses (50 marks)
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