HIV Flashcards
HIV structure
Two identical (+)RNA Enveloped
Three essential enzymes: - reverse transcriptase - integrase - protease Complex - also has regulatory enzymes (immune modulators, regulation of virion production)
Classification of HIV
aka Human T-cell lymphotrophic virus (HTLV)
Retrovirus -> lentivirus subtype
Not an oncovirus
HIV 1 = most prevalent
HIV 2 = West Africa, both cause AIDS
HIV replication
Attachment -> co-receptor required -> fusion
Reverse transcriptase -> DNA -> integrase ->
Transcription -> translation -> processing (protease) ->
Assembly -> budding -> maturation (protease)
HIV tropism
Viral gp120 -> CD4
- Th (CD4+), also monocytes/macrophages, dendritic, glial
Coreceptor necessary for binding
- CCR5 = chemokine receptor (mutation -> resistant to HIV)
- also can use CXCR4
Fusion = gp41 (viral)
Integration of HIV
Fusion -> entry
Reverse transcriptase: three different functions
ssRNA -> RNA-dep DNA -> ssDNA -> RNAse activity -> DNA-dep DNA -> dsDNA
-> nucleus
Integrase necessary for integration
HIV production
Requires activation of T cell (via immune response)
Active transcription -> mRNA -> translation
Protease cleaves -> assembly
HIV RNA disrupted by APOBEC3G but virus inhibits this with Vif
Maturation - after budding, via protease action
HIV latency
Integrates into T cells
- many T cells are latent (ie memory)
- little transcription
Forms reservoir in host
Can also have low levels of virion production (cell stays alive) vs high levels of production -> cell death
HIV mutations
Reverse transcriptase and host RNA-polymerase
- neither has proofreading function
1: 5-10 virions are mutated (1 billion/day)
HIV transmission
Sex: - Anal > vaginal, receptive > penetrative, oral Blood: - IVDU probably highest risk - also needle sticks, occupational Maternal - child: - 25% in transplacental and perinatal (more common) - 25% breastfeeding
Additional risks:
VIRAL LOAD correlates with risk
Mucosal injury or infection (ex STDs)
HIV prevention (the basics)
Condoms
+ prophylactic ARVs effective if high risk
Circumcision - works in some populations
Microbicidals (ie vaginal cream) - in testing
Don’t share needles
Blood supply quality controls
Testing and treatment
HIV pathogenesis
Acute infection = super high viral load, drop in CD4 (infected and inflammatory cell death)
- CD4 cells respond to infection -> activation -> makes more virions (vicious cycle…)
- cytokines, CD8 -> antibodies -> partial immune control (“set point”) ->
Chronic - still actively making virions in lymphoid tissue
Acute HIV presentation
Similar to mono:
- fatigue, fever, headache, sometimes rash
- lymphadenopathy
Diagnose through viral load (super high)
- not yet making antibodies (seroconversion takes 2 months)
HIV “set point”
Transition from acute to chronic infection
- represents partial immune control
- lowest viral production level (will amplify from there as more CD4 activated)
Only true predictor for progression of disease
Chronic HIV infection
Often asymptomatic
Diagnosis - antigen and antibody by ELISA -> Western Blot
Active production of virus in lymphoid tissue (10 billion/day)
- constant mutation to evade immune response (Ab, CD8)
Immune activation
-> kills CD4 (1 billion/day, most through activation-induced)
- HIV proliferates
Slow decline in CD4
Definition of AIDS
Presence of opportunistic infection
HIV+ and CD4 <15% lymphocytes
