Mhr Topic 29: Retroviruses And Hiv

Front 1

Reverse transcription

Back 1

synthesizing DNA from an RNA template

Front 2

Retroviruses (genome, envelope, replication, types)

Back 2

SS + Diploid RNA
Enveloped
reverse transcription, incorporate into host genome, not cytolytic
HTLV-1 and HIV

Front 3

In addition to genome, what is contained in retroviruses capsid?

Back 3

3 enzymes, protease, integrase, and reverse transcriptase.

Front 4

3 genes necessary in all retroviruses

Back 4

Gag - Encodes matrix and capsid proteins and sometimes protease
Pol - Encodes reverse transcriptase, integrase, and protease
Env - Encodes envelope proteins

Front 5

Long terminal repeats (LTR)

Back 5

Flank viral coding sequences. Are regulatory elements which contain strong promoter enhancers which drive transcription of the viral genome. Can be regulated in more complex viruses.

Front 6

Retrovirus replication

Back 6

1) Virus enters cell via fusion and capsid/matrix disassemble
2) Viral RNA is copied into DNA via reverse transcriptase in cytoplasm.
3) DNA/protein complex enters nucleus.
4) DNA is permanently integrated into cellular genome via integrase.
5) Transcription of the Viral DNA is by host RNA Pol 2.
6) Translation occurs and cleaved by viral/host proteases.
7) Viruses assemble and then bud out of cell getting an envelope in a non-cytolyitic fashion.

Front 7

Compare HBV and retroviruses (location of reverse transcription, genome, product structure, transcription template, transcription machinery, error-prone replication)

Back 7

1) Reverse transcription: HBV = Parent cell, HIV = New Host cell
2) HBV = partially dsDNA, HIV = ss+RNA
3) HBV = Partially DS circular DNA (unincorporated). HIV = DS liniar DNA (integrated).
4) HBV = nuclear episome. HIV = Nuclear integrated provirus
5) HBV and HIV both use host RNA pol 2
6) Both have error prone replication.

Front 8

Provirus

Back 8

Retroviral DNA permanently integrated into hosts cellular genome. If infected cell is a germ cell, is referred to as an endogenous retrovirus.

Front 9

3 reasons why endogenous retroviruses are medically important

Back 9

1) Can cause cancer (though rare)
2) Are found throughout the human genome and have helped the genome evolve.
3) Endogenous retroviruses found in other animals are a hurdle in xenotransplantation.

Front 10

Retroviral Transduction

Back 10

When virus incoorperates cellular genes into the viral genome and then transfers them to another cell.

Front 11

3 reasons why retroviral transduction is medically important

Back 11

1) Used to make specialized cell lines for research and drug development.
2) Can be used for gene therapy in the future
3) Major method of retroviral oncogenesis in animals (which has taught us about cell cycle control).

Front 12

3 methods of retroviral oncogenesis

Back 12

1) Transduction of oncogenes
2) Insertional mutagenesis - Can either screw up tumor suppressor genes or the LTRs can cause overexpression of cellular genes
3) Viral regulatory factors may disregulate the cellular genes.

Front 13

HTLV-1 (infection, Disease)

Back 13

1) Infects T cells. STD, transfusion, or vertically via infected breast milk.
2) Most infections are subclinical. Can cause leukemia and HAM/TSP (which are mutually exclusive)

Front 14

HIV1 vs HIV2

Back 14

HIV1 is found worldwide, is more infectious, and more virulent.
HIV2 is found in western africa, and is closer to SIV.

Front 15

HIV (infection, disease)

Back 15

1) Blood and bodily fluids (need 100x more virus than HBV)
2) Acute - About half or so are symptomatic. Flu like with lymphadenopathy. Incubation = 2-4 weeks. Duration = 2 weeks.
Chronic = 100% of cases become chronic. Continuous rapid production and clearance of virus. CD4 cells continually decrease. 50% get AIDs in 10 years if untreated.

Front 16

2 definition of AIDS

Back 16

1) Appearance of one or more set of opportunistic pathogens which rarely cause disease in health individuals.
2) When CD4 counts drop below 200cells/cc of blood.

Front 17

What is the primary receptor of HIV?

Back 17

CD4 receptors on helper Ts, macs, and monocytes. Requires interaction with a coreceptor. Different strains use different co-receptors (which may determine efficacy).

Front 18

Humoral and Cellular immune response to AIDS

Back 18

1) Neutralizing Abs can be detected few weeks after exposure. Abs are strain specific and can be evaded by replication
2) CD 8s kill infected helper Ts. Lose approx half of helper ts early in disease.

Front 19

Neuropathogenisis of HIV

Back 19

HIV enters the nervous system early after infection. NS are distinct from the blood ones (suggesting they have been selected). Infect astrocytes and microglia. This can allow other viruses (especially JC virus) to progress leading to progressive multifocal leukoencephalopathy and death.

Front 20

HIV diagnosis

Back 20

Detection of anti-viral antibodies or by detecting viral RNA in serum via pcr

Front 21

What causes death from AIDS

Back 21

Combination of opportunist infection and weight loss (slim disease).