retroviruses (HIV too)

Question 1

how do retroviruses work?

Answer 1

use reverse transcription to convert RNA –> DNA, integrate into host genome

Question 2

What are the components of a retrovirus structure?

Answer 2

structural protines –> envelop, gag
viral enzymes –> reverse transcriptase, integrase, protease
viral genome –> 2 RNA molecules

Question 3

name some accessory proteins

Answer 3

-tat (tax)= transactivator req for viral gene transcription
-rev (rex)= nuclear exporter
-vif
vpr
vpu (release)
nef

Question 4

whats the life cycle?

Answer 4

1) binding and entry
2) reverse transcription –> in cyto, ERROR prone
3) genome integration –> viral integrase
4) viral gene transcription –> tat transactivator
5) virus assembly and release –> vpu req for virus release

Question 5

HERV- Human endogenous retrovirus

Answer 5

• 8-10% of human genome
• most defective and chill
• may be assoc with cancers

Question 6

AIDS defining cancers

Answer 6

• kaposis (HHV8)
• non hodgkins lymphona (HHV8, EBV)
• Cervical (HPV)

Question 7

what are some challeneges with treating HIV positive cancers?

Answer 7

• atypical path + higher grade tumors
• poorer outcomes
• higher rate of relapse
• rapidly invasive
• develops at younger age

Question 8

what are human diseases assoc with HTLV?

Answer 8

• Adult T cell leuk/lymphoma (ATL)
• HTLV1-assocaited-myelopathy (HAM)
• Uveitis

Question 9

what disease does HAM resemble?

Answer 9

MS –> weakness, stiffness of legs

tropical spastic paraparesis

Question 10

in what demographics do we see HTLV

Answer 10

japanese
caribbean
south america
africa
iran

Question 11

HTLV transmission. On that note, can you detect HTLV in the blood?

Answer 11

• mother-child during breastfeeding
• sex
• infx blood/ needles

** requires direct cell to cell contract. Not seen in blood.

Question 12

Markers for HIV dz in patient

Answer 12

CD4 count correlates to dz progression

Plasma HIV RNA level= virla load= measure of ongoing replicaiton in lymphoid tissue

Question 13

envelope protein markers of HIV? Which is involved in entry?

Answer 13

Gp40, GP120

GP120 binds TCR and CCR5 on t cell surface

Question 14

sup with the CCR5 d32 mutation

Answer 14

protective. 32 bp deletion causing translational frameshift/ truncation that prevents surface expression of CCR5. HIV can’t get into T cell.

Question 15

clinical manifestations of HIV?

Answer 15

initial infection –> mono like, +- aseptic meningitis,

• usu 2-3 weeks post HIV exposure
• occurs in 50% of pt but USUALLY UNRECOGNIZED

Question 16

signs/sx of HIV infection (primary)

Answer 16

fever
fatigue
maculopapular rash
myalgia
HA
pharyngitis
cervical LAD
arthralgia
oral ulcers
weightloss
oral candida

Question 17

basics: opportunistic infection. how can you prevent?

Answer 17

infx that takes advantage of weakened immune sys

usu CD4 <200

try to prevent by restoring CD4 count with antiretrovirals

Question 18

name some opportunistic infx

Answer 18

PCP
kaposi sarcoma
thrush --> considered once it travels from mouth to esophagus
CMV retinitis
CNS toxoplasmosis
extrapulm TB

Question 19

Whats the goal of antiviral therapy? clincally and immunulogically

Answer 19

• inhibit entry/replication
• prevent deterioration of immune sys
• prevent opp infx
• reduce hospitalizations and long term care use

Question 20

HIV has been hard to treat because….

Answer 20

God! Just kidding, viral evolution.

seriously, viral reverse transcriptase is ERROR prone, creates plenty of viral variants that evolve from initial inoculum

one drug is never enough. 2-3 HAART always

Question 21

What are the targets of HAART?

Answer 21

Protease inhibitors
entry inhibitors
reverse transcriptase inhibitors (NRTI, NNRTI)

Question 22

protease inhibitors

Answer 22

-navir

inhibit HIV-1 protease POL GENE –> this cleaves HIV mRNA into functional products
-bonus –> boosts other concentrations because P450 inhibitor

Question 23

side effects of Protease inhibitors

Answer 23

hyperglycemia, GI intolerana, lipodystrophy

indinavir= neuropathy, hematuria
rifampin= potent CYP INDUCER

Question 24

integrase inhibitors

Answer 24

___“tegr”____ (get it, like inTEGRase)

inhibit HIV genome integration into host cell csome by REVERSIBLE INHIBITION OF HIV INTEGRASE

Question 25

major side effect of integrase inhibitors?

Answer 25

increased CK

Question 26

NRTIs

Answer 26

nucleoSide (except Tenofovir= nucleoTide) that lacks 3’OH –> competitively binds reverse transcriptase and terminates DNA chian

must have P activation

Question 27

side effects of NRTIs? Which is used in pregnancy?

Answer 27

Zidovudine in pregnancy
- causes bone marrow suppression –> neutropenia, anemia

lactic acidosis

stocking glove neuropatyh

Question 28

NNRTIs

Answer 28

DO NOT REQUIRE P ACTIVATION

bind to reverse transcriptase at diffferent site from NRTI

Question 29

side effects of NNRTIs. should you use these in pregnancy?

Answer 29

rash
hapatotoxicity
vivid dreams
CNS symptoms

delavirdine and efavirenz are contraincidcated in pregnancy

Question 30

entry/fusion inhibitors

Answer 30

maraviroc –> binds CCR5, blocks gp120

BMS-663068= –> fusion inhibitor

Question 31

how do we dx HIV in the lab?

Answer 31

ELISA followed by western

• can be false neg in first 1-2 months
• can be false positive in infants born to HIV mom due to placental crossing of anti-gp120

Question 32

what infections are seen with CD4< 500

Answer 32

candida
EBV
bartonella henselae
HHV8
cryptosporidium
HPV

Question 33

infections seen in CD4 < 200

Answer 33

PJP
Jc virus reactivation
HIV dementia

Question 34

infections seen in CD4 <100

Answer 34

aspergillus
histoplasma
candida albicans
cryptocococcus
CMV
mycobacterium avium
EBV
toxoplasma gondii