Retroviruses part 2 Flashcards
(27 cards)
how is HIV transmitted?
blood sexual transmission (vaginal and anal) perinatal (intrauterine, peripartum, breast milk)
why are the accessory proteins of HIV important?
six additional proteins that are necessary for replication or pathogenesis (Vif, Vpr, Vpu, Nef, Tat, Rev)
What are the regulatory proteins of HIV?
Tat and Rev
Why are the regulatory proteins of HIV important?
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
What are restriction factors of HIV?
proteins of the virus that combat cellular defenses
Name the restriction factors of HIV
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
what is the receptor that HIV binds to on cells?
CD4
What kind of cells can HIV bind to
CD4 T cells
dendritic cells (cannot be infected however-nevertheless can help w/ virus spread)
macrophages (infected but not killed)
microglia
what is required for membrane fusion in HIV?
CD4 binding
co receptor
M-tropic HIV are responsible for
initial infection and transmission, reside in asymptomatic persons
T tropic HIV are noted in
disease progression–begin to appear at AIDS stage
the coreceptor for M tropic HIV
chemokine receptor CCR5
the co receptor for T tropic HIV
chemokine receptor CXCR4
what explains the strain tropisms of HIV?
the HIV strains have envelope sequences that prefer different co receptors
Which strain of HIV is responsible for person to person transmission?
M tropic virus
Why do some rare people stay seronegative for HIV even with repeated viral exposure?
one explanation could be that they have a 32bp deletion in CCR5 gene (could be heterozygous or homozygous)
the co receptor binding is important for HIV because
it causes the gp41 to snapback and induce membrane fusion
What is the mechanism of T20 C peptides for HIV treatment?
T20 C peptides bind N terminal helical region of gp41 and prevent snapback/fusion of HIV with cell membrane
events that happen after initial HIV infection
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
How does HIV cause disease?
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)
How is viral load of HIV measured?
measuring RNA by PCR
How to diagnose HIV?
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
Available drugs for HIV currently
RT inhibitor (drug resistance fast)
Protease inhibitors
Fusion inhibitor (T20)-expensive, injected
entry inhibitor (CCR5 coreceptor antagonist)
Integrase inhibitor
HAART
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
