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29 Cards in this Set

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Are retroviruses enveloped or nonenveloped?
Enveloped

- have single glycoprotein called "Enveloped" (Env) protruding from viral membrane
What are the 3 genes that all retroviruses have?
1. gag - (group specific antigen). Forms capsid

2. pol - makes 3 enzymes made by retrovirues: protease, integrase, and reverse transcriptase.

3. env: makes envelope protein
Does Reverse Transcriptase (RT) have proof reading capability?
No, thus retroviruses like HIV can mutate quickly.
What does the enzyme integrase do for retroviruses?
Integrates DNA into host's genome and allows retrovirus infections to persist FOR LIFE.
Where does HIV integrate into human host chromosomes?
HIV can integrate anywhere, but tends to integrate in active genes. This can potentially lead to activation of oncogene.
What is the role of protease for HIV?
Protease cleaves the polypeptide into many component parts, including RT, integrase, an viral core proteins.

Protease is an IMPORTANT DRUG TARGET
What 1 of 2 conditions does an HIV+ patient need to meet in order to have AIDS?
Either:

1. CD4 counts fall below 200/mL

2. Have an AIDS defining illness
When was the virus responsible for AIDS discovered?

When was first reported case?
Discovered: 1983

First reported case: June 1981
In the US, how many people are HIV+?

Have AIDS?

How many new cases / year?
HIV+: 1.1 Million (20% unaware)

AIDS: 470,000

56,000 new cases / year
How many deaths / year are caused by AIDS?
20,000
How many total people worldwide have been infected with HIV?

How many deaths have resulted?

How many new cases / year?
>60 million have been infected

>20 million deaths

>2.5 million new cases / year
How many people worldwide die / year from AIDS?
>2 million deaths / year from AIDS
What is the leading cause of death in Africa?
HIV (highest rate in Botswana)
Where did HIV-1 arise from?

HIV-2?
- HIV-1 arose from chimp-human transmission

- HIV-2 arose from sooty mangabey-human transmission
What virus probably gave rise to HIV?
Simian Immunodeficiency Virus (SIV)
What is zoonosis?
A disease or infection naturally transmitted between vertebrate animals (the reservoir) and humans.
What 2 characteristics of HIV make treatment with only 1 drug likely to fail?
1. Its high replication rate (10^10) new virus particles made per day

2. High Error Rate: Reverse transcriptase makes error 1 /10,000 bases.

This means that every base in the viral genome mutates to every other possible base, EVERY DAY
What is the primary treatment for HIV?
Highly Active Anti-Retroviral Therapy (HAART). Usually 3 different drugs that work by different mechanisms

- multi drug regiment

- Includes drugs that block protease (inhibits viral maturation), entry, integrase, and RT.
What are the steps in HIV entering a cell?
1. HIV engages CD4 receptor via env (gp120)

2. Env then binds co-receptor (either CCR5 or CXCR4)

3. gp41 fusion peptide exposed, inserts into cell membrane

4. gp41 helical regions fold back on each other to bring membranes together, FUSION
What are the 4 classes of antiretroviral agents?
1. RT Inhibitors

2. Protease Inhibitors

3. Integrase Inhibitors

4. Entry Inhibitors (NEW)
What are the 2 main measures of HIV disease progression?
1. CD4+ T cell count (AIDS = <200)

2. Level of HIV RNA in plasma ("viral load")
What are the symptoms and characteristics of Acute HIV?
- Occurs 2-6 wks following infection. Lasts 1-3 wks

- Mono like symptoms

- Extremely highly circulating virus

- GALT decimated. Bacteria enter bloodsteam. Immune response helps to spread HIV.

- VERY INFECTIOUS during this time
What is the period following Acute HIV infection?
Clinical Latency

- viral load decrease to ~30,000/ml

- usually asymptomatic

- CD4+ count slowly declines (7-10 years)
What polymorphism account for the "exposed-uninfected" individuals who do not contract HIV?
delta32 - ccr5 polymorphism
What are the 4 categories of HIV infected individuals (with regard to disease progression)?
1. Exposed - Uninfected - ccr5 polymorphism

2. Rapid Progressors - progress to AIDS quickly, 1-3 years

3. Long term nonprogressors: 5% of ppl with HIV >20 years who don't progress to AIDS

4. Elite Controllers - subset of long term nonprogressors who have virus loads below level of detection
What are the cellular characteristics of HIV?
- retrovirus

- enveloped

- 2 copies of +ssRNA
What are the 2 types of RT inhibitors?
1. Nucleoside RTI (NRTI) - look like nucleotides, but stop elongation when incorporated

2. Non-Nucleoside RTI (NNRTI) - bind to RT at a different site than NRTI

Note: viruses resistant to NRTI can still be sensitive to NNRTIs
Why does drug recycling not work for HIV?
Because HIV has latent reservoirs in memory cells that guarantee lifetime persistence/resistance
How does HIV genotyping aid in treatment?
- Doctors can know which strain of HIV the pt has, whether resistant.

- Prescribe Tx accordingly