Micro: HIV Path and AIDS

Question 1

What is the classification of HIV?

Answer 1

retroviridae family
lentivirus genus
complex

Question 2

When is someone considered to have AIDS, not just HIV?

Answer 2

CD4 <200 or AIDS defining clinical dx (OI or cancer)

avg to get here is 10 yrs

Question 3

How does HIV subvert the immune system?

Answer 3

infecting CD4 T cells that normally act in immune response

activating immune system and inducing cytokines that virus uses to its own replication advantage

Question 4

What is the basic structure of the HIV virion?

Answer 4

envelop glycoproteins gp120 (binds to CD4 receptor) and gp41 (causes fusion w host cell membrane)
capsid protein p24

Question 5

What is required for HIV attachment to host cells?

Answer 5

gp120 binds CD4 receptor on T cells (also monocytes, macrophages and APC dendritic at low concentrations)
gp41 helps w fusion
co-receptors are CCR5 and CXCR4

Question 6

What is the basic life cycle of HIV?

Answer 6

viral core into cytoplasm - reverse transcription of ssRNA to dsDNA - transport to nucleus - circularization of DNA - integration - production of viral RNA and transport out of nucleus - production of viral proteins - capsid assembly - packaging and cleavage to release by budding

Question 7

What is a big difference between early HIV and late HIV?

Answer 7

early primarily CCR5 tropic (slower loss of CD4)

late primarily CXCR4 tropic (rapid loss of CD4)

Question 8

What is the immune response to the initial entry of HIV into mucosal surfaces?

Answer 8

bone marrow derived dendritic cells pick it up, take to paracortical regions of lymphoid organs and delvers to CD4 T cells, DCs play little role after this

Question 9

What are clinical features of acute HIV inf?

Answer 9

10-30 days post exposure, lasts t eliminate

virus set-point determines rate of CD4 loss

Question 10

How is acute HIV inf diagnosed?

Answer 10

HIV Ab negative on ELISA and western blot becomes + over time
plasma HIV p24 + becomes - over time
RNA can decline to undetectable levels over time

Question 11

What are pts most vulnerable to at certain CD4 counts?

Answer 11

over 200: h. zoster, tb, ITP, pneumococcus
less than 200: PCP, thrush, KS
less than 100: toxo, crypto, lymphoma, candida, esophagitis
less than 50: MAC, CMV, PML

Question 12

What is the “window period”?

Answer 12

in primary HIV inf - time from inf to production of antibodies, about 4-6 mos

Question 13

What goes wrong with the t helper response to HIV?

Answer 13

early deletion of HIV specific

anergy due to high antigen burden, antigen induced apoptosis or defect in antigen presentation

Question 14

Where are antibodies to HIV directed?

Answer 14

V3 loop, CD4 binding site on gp120, coiled-coil structure on gp41

Question 15

What is a hallmark of progressive HIV infection and quite paradoxical?

Answer 15

chronic activation of immune system - don’t know why (ciruclating microbial products from GI tract?)

Question 16

What is important about the nef gene?

Answer 16

virus w deleted nef leads to low viral load and slow loss of CD4

Question 17

What are host factors that can affect immunity to HIV?

Answer 17

CCR5 deletion: homozygous can still get infected w CXCR4, heterozygous slows dz progression
CCR5 promoter mutations

Question 18

What are AIDS defining malignancies?

Answer 18

kaposis sarcoma (HHV-8)
high grade non hodgkins (EBV)
invasive cervical cancer (HPV)

Question 19

What are the different targets of antiretroviral therapy?

Answer 19

viral reverse transcriptase: nucleoside and analogues = NRTI chain terminators, non nucleoside inhibitors = NNRTI competitive inhibitors
viral protease, receptor antagonists, fusion inhibitors, integrase inhibitors, maturation inhibitors

Question 20

What are the 3 phases of response to HAART?

Answer 20

first - loss of productively infected cells
second - loss of long-lived infected cells and release of trapped virions from dendritic cells
third - irreducible reservoir of resting CD4 cells w replication competent virus

Question 21

What is the effect on quantity of T cells after starting HAART?

Answer 21

initial rapid rise in CD4, followed by slower rise

elevated CD8 takes longer to normalize - always remains slightly elevated