HIV Flashcards
Describe retroviruses.
enveloped
single stranded (+)
two copies
How do retroviruses replicate?
through DNA intermediate using reverse transcriptase
Which two retrovirus cause disease?
Deltaretrovirus - complex (HTLV)
Lentivirus - complex (HIV-1, HIV-2)
What is RNA dependent DNA pol used for?
A DNA polymerase enzyme that catalyzes the process of reverse transcription.
What is integrase
viral protein that helps entry
What three major proteins do retroviruses have?
gag
pol
env
What are the 6 accessory genes for HIV1?
tat rev nef vif vpr vpu
Where does the retrovirus assemble and bud?
plasma membrane
Gag encodes for?
Structure:
matrix
capsid
nucleocapsid
Pol encodes for?
enzymes
reverse transcriptase (acts in cytoplasm)
integrase (integrates provirus DNA into host DNA)
protease (cleaves GAG protein; inhibits replication cycle)
Env encodes for?
Envelope proteins:
Surface Glycoproteins
Transmembrane Protein
What are the two regulatory proteins for HIV?
tat (transactivator - increase transcription)
rev (regulator of viral expression)
Is nef (negative regulation factor) a regulator?
NO, it down regulates CD4 and MHC class II
Why would nef downregulate CD4 and MHC II?
Virus wants to replicate before cell is attacked.
What is the function of vpu (Viral protein U)?
promotes degradation of CD4 and enhances release of virus from cell membrane
What is the function of vpr (Viral Protein R)? ***
- transports DNA to nucleus
- increases virion production
What is the function of vif (viral infectivity)? ***
affects particle infectivity
Which two coreceptors are used for binding?
CCR5 (CD4 and macrophages)
CXCR4 (CD4 and T cell lines)
Viral DNA is formed be what process?
reverse transcription
What regulates transcription?
tat (transactivator)
What allows export of virus from nucleus?
rev (regulator of viral expression)
What helps virus release from cell membrane?
vpu (viral protein U)
How are HTLVs transmitted?
blood, sexual, vertical
HTLV-2 is more common in what population?
IV drug users
Where is HTLV-1 prevalent?
Japan, Caribbean, tropics
What are the clinical manifestations of HTLV-1?
inflammation spinal cord atrophy hyper-reflexivity leg weakness urinary and fecal incontinence
What is HTLV-2 associated with?
atypical T-cell hairy leukemia
Where did HIV come from?
chimpanzee (SIV-simian immunodeficiency virus)
List the four groups of HIV-1.
Group M - major
Group N - man from Cameroon
Group O - outlier “West Central Africa”
Group P - woman from Cameroon (gorilla simian immunodeficiency)
How many clades (subtypes) of group M are identified?
9 (A, B, C, D, E, F, G, H, I, J, K)
HIV-2 has how many groups?
8 (A, B, C, D, E, F, G, H)
Which receptor does an M-tropic R5 virus use?
CCR5
Which receptor does a T-tropic X4 virus use?
CXCR4
Which protein is embedded in the membrane?
Gp41
Which protein is the head of the stalk?
Gp120
Describe the two types of conformational changes due to gp41 and gp120.
GP120 binds to Tcell and promotes binding of chemokine receptor.
GP41 undergoes a conformational change that exposes the fusion peptide which inserts into the Tcell membrane.
Patients initiating treatment for Tb should also be screened for what infection?
HIV
What is the 2-step laboratory test to diagnose?
Serum ELISA
confirmed by Western blot or Immunofluorescense
What are some alternative tests for initial diagnosis?
rapid oral antibody test
results in 5 to 40 minutes
What are some tests that may be performed post-diagnosis?
Quantition of virus in blood: HIV-1RT-PCR
Early marker of infection: Western blot for p24 antigen
correlate of HIV disease: CD4/CD8 Tcell ratio
Be able to read western blot
Negative: total absence of bands associated with HIV1 (gp160/120, p24)
Positive: presence of at least 2 of the following bands:
p24
gp41
gp120/160
How does a western blot work?
Control lane with proteins that are present in HIV-1
Patient’s serum lane is compared for bands
+Positive Must have at least 2 bands
p24
gp41
gp120/160
What does p24 band indicate in HIV infection?
early infection
What is acute HIV infection?
time between infection and seroconversion
- must see detectable HIV RNA or DNA or p24
- cannot be antibody based test
