retroviruses (HIV too) Flashcards
(34 cards)
how do retroviruses work?
use reverse transcription to convert RNA –> DNA, integrate into host genome
What are the components of a retrovirus structure?
structural protines –> envelop, gag
viral enzymes –> reverse transcriptase, integrase, protease
viral genome –> 2 RNA molecules
name some accessory proteins
-tat (tax)= transactivator req for viral gene transcription
-rev (rex)= nuclear exporter
-vif
vpr
vpu (release)
nef
whats the life cycle?
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
HERV- Human endogenous retrovirus
- 8-10% of human genome
- most defective and chill
- may be assoc with cancers
AIDS defining cancers
- kaposis (HHV8)
- non hodgkins lymphona (HHV8, EBV)
- Cervical (HPV)
what are some challeneges with treating HIV positive cancers?
- atypical path + higher grade tumors
- poorer outcomes
- higher rate of relapse
- rapidly invasive
- develops at younger age
what are human diseases assoc with HTLV?
- Adult T cell leuk/lymphoma (ATL)
- HTLV1-assocaited-myelopathy (HAM)
- Uveitis
what disease does HAM resemble?
MS –> weakness, stiffness of legs
tropical spastic paraparesis
in what demographics do we see HTLV
japanese caribbean south america africa iran
HTLV transmission. On that note, can you detect HTLV in the blood?
- mother-child during breastfeeding
- sex
- infx blood/ needles
** requires direct cell to cell contract. Not seen in blood.
Markers for HIV dz in patient
CD4 count correlates to dz progression
Plasma HIV RNA level= virla load= measure of ongoing replicaiton in lymphoid tissue
envelope protein markers of HIV? Which is involved in entry?
Gp40, GP120
GP120 binds TCR and CCR5 on t cell surface
sup with the CCR5 d32 mutation
protective. 32 bp deletion causing translational frameshift/ truncation that prevents surface expression of CCR5. HIV can’t get into T cell.
clinical manifestations of HIV?
initial infection –> mono like, +- aseptic meningitis,
- usu 2-3 weeks post HIV exposure
- occurs in 50% of pt but USUALLY UNRECOGNIZED
signs/sx of HIV infection (primary)
fever fatigue maculopapular rash myalgia HA pharyngitis cervical LAD arthralgia oral ulcers weightloss oral candida
basics: opportunistic infection. how can you prevent?
infx that takes advantage of weakened immune sys
usu CD4 <200
try to prevent by restoring CD4 count with antiretrovirals
name some opportunistic infx
PCP kaposi sarcoma thrush --> considered once it travels from mouth to esophagus CMV retinitis CNS toxoplasmosis extrapulm TB
Whats the goal of antiviral therapy? clincally and immunulogically
- inhibit entry/replication
- prevent deterioration of immune sys
- prevent opp infx
- reduce hospitalizations and long term care use
HIV has been hard to treat because….
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
What are the targets of HAART?
Protease inhibitors
entry inhibitors
reverse transcriptase inhibitors (NRTI, NNRTI)
protease inhibitors
-navir
inhibit HIV-1 protease POL GENE –> this cleaves HIV mRNA into functional products
-bonus –> boosts other concentrations because P450 inhibitor
side effects of Protease inhibitors
hyperglycemia, GI intolerana, lipodystrophy
indinavir= neuropathy, hematuria rifampin= potent CYP INDUCER
integrase inhibitors
___“tegr”____ (get it, like inTEGRase)
inhibit HIV genome integration into host cell csome by REVERSIBLE INHIBITION OF HIV INTEGRASE
