Retroviruses - 2013 (FN) [Compatibility Mode]

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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Retroviruses - 2013 (FN) [Compatibility Mode]