Retroviruses part 2

Question 1

how is HIV transmitted?

Answer 1

blood
sexual transmission (vaginal and anal)
perinatal (intrauterine, peripartum, breast milk)

Question 2

why are the accessory proteins of HIV important?

Answer 2

six additional proteins that are necessary for replication or pathogenesis (Vif, Vpr, Vpu, Nef, Tat, Rev)

Question 3

What are the regulatory proteins of HIV?

Answer 3

Tat and Rev

Question 4

Why are the regulatory proteins of HIV important?

Answer 4

they are required for viral replication
Tat: transactivator of transcription: necessary for transcription in addition to NFkB binding to U3
Rev: regulator of virion expression: allows for structural gene expression by inducing transport of unspliced RNA from nucleus to cytoplasm

Question 5

What are restriction factors of HIV?

Answer 5

proteins of the virus that combat cellular defenses

Question 6

Name the restriction factors of HIV

Answer 6

Vif: virion infectivity factor: induces the degradation of a cellular antiviral protein called deoxycytidine deaminase, which usually goes into newly made virions and causes mutations in viral genome

Vpu: induces virion release from cell by inhibiting host protein called tetherin

Question 7

what is the receptor that HIV binds to on cells?

Answer 7

CD4

Question 8

What kind of cells can HIV bind to

Answer 8

CD4 T cells
dendritic cells (cannot be infected however-nevertheless can help w/ virus spread)
macrophages (infected but not killed)
microglia

Question 9

what is required for membrane fusion in HIV?

Answer 9

CD4 binding

co receptor

Question 10

M-tropic HIV are responsible for

Answer 10

initial infection and transmission, reside in asymptomatic persons

Question 11

T tropic HIV are noted in

Answer 11

disease progression–begin to appear at AIDS stage

Question 12

the coreceptor for M tropic HIV

Answer 12

chemokine receptor CCR5

Question 13

the co receptor for T tropic HIV

Answer 13

chemokine receptor CXCR4

Question 14

what explains the strain tropisms of HIV?

Answer 14

the HIV strains have envelope sequences that prefer different co receptors

Question 15

Which strain of HIV is responsible for person to person transmission?

Answer 15

M tropic virus

Question 16

Why do some rare people stay seronegative for HIV even with repeated viral exposure?

Answer 16

one explanation could be that they have a 32bp deletion in CCR5 gene (could be heterozygous or homozygous)

Question 17

the co receptor binding is important for HIV because

Answer 17

it causes the gp41 to snapback and induce membrane fusion

Question 18

What is the mechanism of T20 C peptides for HIV treatment?

Answer 18

T20 C peptides bind N terminal helical region of gp41 and prevent snapback/fusion of HIV with cell membrane

Question 19

events that happen after initial HIV infection

Answer 19

HIV encounters DC cells, which carry HIV to lymph nodes

in lymph nodes, HIV infects T cells

HIV replicates to high levels and produces viremia

in asymptomatic phase, FDC traps the virus and reduces viremia–however, lymph nodes (especially GALT) have replication

Question 20

How does HIV cause disease?

Answer 20

directly kills CD4 T cells
indirectly affect infected CD4 cells (immune response)
weakening of immune system fxn (CD4 Tcell fxn changed, infected macrophages fxn changed)

Question 21

How is viral load of HIV measured?

Answer 21

measuring RNA by PCR

Question 22

How to diagnose HIV?

Answer 22

serology (not useful for newly infected, not to be relied on until 4-6 wks after infection)–Ab ELISA, Ag ELISA, Western

RNA RT-PCR to detect virus in blood

RTPCR: quantitate virus in blood, for viral load

Question 23

Available drugs for HIV currently

Answer 23

RT inhibitor (drug resistance fast)
Protease inhibitors
Fusion inhibitor (T20)-expensive, injected
entry inhibitor (CCR5 coreceptor antagonist)
Integrase inhibitor

Question 24

HAART

Answer 24

highly active anti retroviral therapy

cocktails of different HIV inhibitors
can eliminate virus production in some people for lots of years–virus not seen in plasma, increases CD4 counts. Long term however-toxicity

Question 25

Estimated time for clearing free virus and infected T cells with HAART

Answer 25

2 months

Question 26

How long does it take to clear HIV from infected memory T cells?

Answer 26

more than 75 yrs

Question 27

downsides of HAART

Answer 27

not all pts responsive
hard to follow regimen
long term has toxicity
there’s an inaccessible pool of virus in memory T cells