Immuno 8: HIV Infection

Question 1

Which cells does HIV mainly infect ?

Answer 1

CD4+ T helper cells

Question 2

Name 2 co-receptors of T cells that HIV-1 needs to bind to in order to cause infection ?

Answer 2

CCR5 or CXCR4

Question 3

List 3 routes of transmission of HIV ?

Answer 3

Sexual- especially anal sex
Infected blood- Needle sharing, transfusions, blood products
Vertical transmission- Mother to child during birth or breast feeding

Question 4

At which 2 parts of HIVs lifecycle do mutations occur that create variation in its genome ?

Answer 4

1- When reverse transcriptase converts viral RNA into DNA

2- When viral DNA is transcribed in the host’s nucleus into viral RNA

Question 5

List 4 possible mechanisms that can could cause long term non-progression in HIV infected patients ?

Answer 5

CCR5 mutation
Effective CTL & HTL response
Infection with attenuated strain of HIV
Secretion of chemokines that block HIV entry into cells - MIP-1a

Question 6

Which tests are done for HIV screening, diagnosis, severity ?

Answer 6

HIV antibodies on ELISA (screening test)
HIV antibodies on Western blot (Confirms diagnosis)
Viral RNA on PCR (viral load)
CD4+ count on flow cytometry

Question 7

Why does HAART not eliminate HIV infection ?

Answer 7

There is a reservoir of HIV in resting CD4+ cells

Question 8

List 3 classes of anti retroviral drugs and an example of a drug in each ?

Answer 8

Nucleoside reverse transcriptase inhibitors (NRTI)- Zidovudine
Nucleotide RTI- Tenofovir
Non-NRTI- efavirenz
Protease inhibitor- ritonavir

Question 9

what are the receptors and coreceptors for HIV

Answer 9

CD4 molecule = receptor for HIV-1

most infecting strains also need co-receptors CCR5/CXCR4 to enter cells

Question 10

what are the features of natural HIV immunity

Answer 10

mobilised within hours of infection + involves:

• inflammation
• non-specific activation of macrophages
• non-specific activation of NK cells and complement
• release of cytokines and chemokines
• stimulation plasmacytoid dendritic cells by toll-like receptors

Question 11

what are the features of acquired HIV immunity

Answer 11

anti-gp120
anti-gp41
non-neutralising anti-p24 gag IgG

Question 12

what are the effects of HIV-1 on CD8+ T cells

Answer 12

CD4+ T cells are disabled (anergised) by the virus
so monocytes and dendritic cells are not activated by CD4+ T cells and cannot prime naive CD8+ T cells
CD8+ T cell and B cell responses are diminished without help from CD4+
CD4+ memory cells lost
infected monocytes and dendritic cells will be killed by the virus or by CD8+ T cells

Question 13

what is the life cycle of HIV

Answer 13

attachment and entry 
reverse transcription and DNA synthesis 
integration 
viral transcription 
viral protein synthesis 
assembly and release of the virus 
maturation

Question 14

what is the clinical course of HIV

Answer 14

median time from HIV infection to development of AIDS = 8-10 years
viral burden predicts disease progression
rapid progressors take 2-3 years
long-term non-progressors have stable CD4+ counts and no symptoms after 10 years
exposed-seronegatives (ESN) = people who are repeatedly exposed to HIV but do not seroconvert

Question 15

list some possible mechanisms for long term non-progression in HIV

Answer 15

host genetics:
- slow progressor of HLA profile
- mannose binding lectin alleles
heterozygosity for 32-bp deletion in chemokine receptor CCR5

host immune respone factors:

• effective CTL + HTL responses
• secretion of CD8 antiviral factor
• secretion of chemokines that block HIV co-entry receptors CCR5 + CXCR4

virologic factors:
- infection with attenuated strains of HIV

Question 16

how can we detect HIV

Answer 16

anti-HIV antibodies (ELISA) - screening test
viral load - viral RNA by PCR
HIV antibody western blot - confirmatory test
CD4+ T cell counts - flow cytometry

Question 17

describe HAART regimens

Answer 17

increases CD4+ T cell counts
- initial rise due to redistribution of memory T cells
- later rise due to thymic naive T cells
improvement in host defences

note: HAART doesn’t eliminate HIV because there is a reservoir in resting CD4+ T cells

2 x nucleoside reverse transcriptase inhibitors (NRTI)
1 X NNRTI or booster protease inhibitor (PI)

Question 18

when is HIV treatment started

Answer 18

all symptomatic patients
all CD4+ counts <200 cells/ microL
CD4 count 200-350 cells/microL

Question 19

features of HIV

Answer 19

genes made of RNA molecules
replicates inside the cell using reverse transcriptase to convert RNA to DNA
primary insects cells of the immune system causing immunodeficiency and AIDS
octahedral structure
genome is diploid
contains 9 genes
encodes 15 proteins