Retroviruses I/II and HIV Flashcards
Describe the general retrovirus structure.
- Enveloped + env genes (gp41/gp120)
- Gag genes = MAtrix, CApsid, NucleoCapsid, PRotease [group-specific)
- 2 copies of +ssRNA = “diploid” genome, which accounts for recombinant potential
Describe the SIMPLE retrovirus.
From 5' to 3' +ssRNA: -R = repeat sequence -U5 = unique to 5' end -gag gene -pol gene = RT, integrase (IN) [in HIV, PR in this region] -env gene = SU [HIV = gp120], TM [HIV = gp1] -U3 = unique to 3' end -R = repeat sequence ONLY ONCE SPLICE FOR ENV GENES
Describe COMPLEX retroviruses [like HIV].
same as simple (5’-R, U5, gag, pol, env, U3, R-3’) plus accessory proteins for MULTIPLE splicing in env region
Reverse transcription in retroviruses takes place in the _______, making dsDNA.
cytoplasm
In retroviruses, only ____ of the viral RNA is uncoated at first because need to make ____ and ____.
RT, IN
In retroviruses, why is integrated DNA longer than viral RNA? What is an LTR? What is this integrated DNA called?
- Because U5/U3 are repeated on each end
- LTR = long terminal repeat = U3/R/U5
- provirus
What 2 polymerase functions does retrovirus RT have? What is one other important characteristic they have?
- RNA-dependent DNA polymerase (–ssDNA)
- DNA-depended DNA polymerase (to make dsDNA)
- characteristic = error-prone polymerase causes increase drug resistance!!
Many retroviruses can’t cross the ______ and need _____ into order to integrate DNA. What is the exception?
- nuclear membrane
- cellular division
- HIV CAN CROSS NUCLEAR ENVELOPE; therefore can integrate in cells that don’t rapidly proliferate
Name a drug to target for:
(a) integrase
(a) Raltegravir
b
Which part of the retrovirus integrated DNA is an enhancer/promotor sequence that binds TF; which end? In HIV, what TF binds this region? What transcribes the provirus?
- U3 region; only the 5’ LTR is transcriptionally active
- NFkB (only in activated T cells)
- HOST RNA POLYMERASE
Most abundant protein made is the ____ protein; how is pol produced? When are these proteins cleaved?
- gag protein
- about 5% of time, RNA polymerase II (host) ignores the stop codon, and transcribes gag-pol as one protein
- at maturation (outside host cell, after budding)
What is the precursor to env proteins gp41 and gp120? What cleaves this precursor polyprotein?
gp160; host polymerase
To package proteins for the cell surface (still polyproteins!!) the gag region contains a signal, ____. ______ removes this signal in env proteins.
- Psi
- Splicing
What are non-transforming retroviruses?
like RSV; take 6month to 1 year to appear; they either:
(1) PROMOTOR INSERTION = retrointegrate (backwards) their DNA into a promotor region and U3 acts a promotor to constitutively transcribe host genes downstream of LTR that are being transcribed (too much!)
(2) ENHANCER INSERTION = LTR acts as enhancer to inappropriately turn on genes that are off (wrong time!)
What are transforming retroviruses?
acute; cause tumors within weeks; carry mutated copy of cellular gene that is turned on = oncogene (Src)
Which 4 groups are most likely to have opportunistic infections with HIV?
Haitians
Heroin Addicts
Hemophiliacs
Homosexual men
What are the 3 routes of HIV transmission?
blood
sexual transmission
perinatal transmission
How many extra proteins does HIV have? What are they?
6
- Tat = transactivator of transcription
- Rev = regulator of virion expression (allows export of mRNA to cytoplasm)
- Vir = virion infectivity factor = deoxycytidine demaninase; causes cellular antiviral protein to be degraded
- Vpu = promotes virion release by inhibiting tethrin
- Nef
- Vpr
What are HIV tropisms? Name the 4 cells HIV infects.
- M-tropic is for marcrophages
- T-tropic is for primary T-cells and T-cell lines; associated with disease progression to AIDS
- CD4 T-helper cells, DCs, Macrophages, Microglia
What are the 2 co-receptors and where are they most prevalent? Which HIV tropism causes the most concern? Why?
- CCR5 = M-tropic HIV (R5-tropic); natural chemokines RANTES, MIP1∂, MIP1ß
- CXCR4 = T-tropic HIV (X4-tropic); natural ligand SDF1
- M-tropic virus; because source of person-to-person contact
Why are some individuals seronegative for HIV despite high risk behavior?
∆32:∆32 CCR5 coreceptor mutation
