Microbiology-HIV Virology Flashcards Preview

Multisystems I > Microbiology-HIV Virology > Flashcards

Flashcards in Microbiology-HIV Virology Deck (21):
1

What are the physical characteristics of HIV?

Lipid membrane: gp41 anchoring glycoprotein, gp120 docking glycoprotein. Within capsid: 2 RNA copies, reverse transcriptase, integrase

2

What are the different types of HIV?

HIV-1 is worldwide and HIV-2 is mostly in western Africa. HIV-1 has M (most variation: ABCDE), O and N groups.

3

What are the HIV receptor/coreceptors?

CCR5 is the primary receptor and CD4 is the primary coreceptor. CXCR4 is the less common receptor, but is more widely expressed on CD4 cells and indicates more widespread infection.

4

Cells that are affected by HIV

CD4+ T-cells get the active infection, dendritic cells transfer live virions and macrophages are typically latently infected.

5

Where does 95% of HIV transmission occur?

Vaginal and GI mucosa. Inner male foreskin. In these tissues, there is a high concentration of activated T-cells expressing CD4 and CCR5, making them easy targets for HIV infection. Note that T-cell activation is increased in state of sexually transmitted disease.

6

How does HIV transmission occur?

Contact with mucosal Langerhans cell -> Antigen presented to CD4+ T-cell by Langerhans cell -> Local lymph node migration -> Viral explosion in local lymph node -> Disseminated infection to other lymph nodes after a few weeks

7

3 stages of HIV infection

1) Primary infection with viremia and CD4 proliferation 2) Latency with slowly dropping T-cell count 3) Final stage w/T-cell count < 200.

8

AIDS defining illnesses

CMV retinitis, Kaposi sarcoma, Toxoplasmosis, Hairy leukoplakia, Pneumocystis pneumonia, Thrush.

9

How does HIV replication happen within the cell?

Viral attachment by gp120 binding of CD4 and CCR5 -> gp41 fusion peptide burrows into cell membrane ->  -ssRNA released -> Reverse transcriptase makes dsDNA, Vpr and preintegration complex -> dsDNA goes to nucleus as Vpr allows it to pass through nuclear pores -> Integrates w/host DNA via the enzyme integrase -> Host machinery transcribes HIV DNA to RNA -> mRNA -> Viral protein -> Once all proteins and RNA are made they come together at the membrane and the virus is released from the surface of the cell membrane -> Gag precursor protein is cleaved to form matrix and capsid protein -> HIV becomes infectious

10

3 things to remember about HIV’s reverse transcriptase?

1) It has RNase H that degrades RNA as it transcribes 2) 2 types of polymerase activity (RNA-dependent DNA and DNA-dependent DNA) 3) Transcription occurs in cytoplasm

11

Why does HIV mutate so easily?

The reverse transcriptase can jump strands, causes errors during transcription and mutation rate is high.

12

In addition to letting HIV get into the nucleus, how does Vpr enhance HIV replication?

It induces cell-cycle arrest so viral replication can utilize all host cell resources.

13

Where does HIV transcription initiate?

cyc T and CDK9 bind Tat -> Tat undergoes a conformational change and can now bind LTR gene’s “TAR”, the transcription initiation factor -> TAT + TAR phosphorylates and activates RNA polymerase -> HIV transcription 

14

How do the HIV transcripts control when it gets out of the nucleus?

Rev Response Elements (RRE) are responsible for bringing transcripts out of the nucleus that cannot do it on their own.

15

What does rev do after it is transcribed?

It binds to importin, and then gets back into the nucleus where it binds to RRE on the RNA transcripts and takes them out of the nucleus and into the cytoplasm for translation.

16

How does the HIV RNA transcript get translated?

1) Pol precursor protein breaks up to form the protease, reverse transcriptase and integrase 2) Gag precursor assembles on virion exit as p24 3) Vif: degrades APOBEC3G so it can’t induce mutations that stop HIV replication 4) Vpr 5) Tat 6) Rev 7) Vpu: binds and degrades CD4 and tetherin so virions don’t get stuck on host cell when budding 8) Nef: enhances HIV synthesis, activates T cells, internalizes CD4, stimulates viral spread.

17

What is the course of HIV infection?

PHI (Primary HIV infection): acute HIV syndrome with wide dissemination of virus and seeding of lymphoid organs. LATENCY: subclinical replication and decrease in T-cell number. 

18

Why is it so difficult to generate a vaccine for HIV?

High mutation rate with reverse transcriptase, circulating recombinant forms (in cells infected with multiple strains) and replication in billions of cells in millions of people.

19

Tests to consider to diagnose someone with HIV in the primary infection stage

p24 ELISA and RT-PCR for viral RNA

20

Tests to consider to diagnose someone with HIV who is in the chronic latent stage

HIV ELISA + Western Blot because it takes weeks to months for seroconversion to occur.

21

What aspects of HIV replication do the anti-retrovirals target?

Entry (fusion inhibitors), reverse transcriptase (nucleoside inhibitors or non-nucleoside reverse transcriptase inhibitors), integrase blockers and protease inhibitors.