HIV Flashcards
which viral class does HIV belong to according to the baltimore scheme?
class 6: reverse RNA, enveloped
Explain the two types of retroviridae
- exogenic: viral genome holds all information needed for the complete sequence of events connected to infection, genome can also contain onco-genes
- endogenous:viral genome lacks essential information for performing a complete and productive infection cycle –> helper retrovirus required
Name the genus of HIV. Is HIV exogenic or endogenous?
lenti virus, exogenic
what are transposons?
transposable genetic elements –> sequences that can move from one position in the genome to another
what is responsible for most of the observed mutations and genetic rearrangements?
transposons
how are transposons controlled?
tranposons controll their own transposition function: either cis acting or trans acting
describe the infection cycle of HIV
- receptor attachment (CD4)
- entry receptor binding
- fusion
- capsid release
- Reverse transcription in capsid
- microtubule transport of capsid to nucleus
- nuclear entry
- integration –> latency
- transcriotion
- export of spliced mRNA and gRNA
- spliced mRNA used for various processes in cell (vpu, bpr, nef…)
- assembly
- budding cia ESCRT
- maturation
Name cellular components and their function and by which viral factor they are inhibited during HIV infection
cell factor + function –> inhibited by viral factor
- SAMDH1 inhibits reverse transcription –> vpx
- foreign DNA silencing —> vpr
- CD4, tetherin for MHC I formation –> vpu, nef
- ung for G2/M cycle –> arrest by vpr
- APOBEC –> vif
which receptors play a role in HIV infection
CD4 receptor is primary
what does the CD4 receptor look like?
fibronectin type III domain with beta sandwich fold closely related to immunoglobulin fold
which HIV structure is recognized by CD4? What happens upon binding?
GP120 –> binding to CD4 leads to changes in the position of several loop to expose the chemokine receptor binding site
describe the model for HIV entry
native trimer gp120 binds to CD4 –> T20 binding site exposure –> CoR binding –> fusion peptide insertion –> 6 helix bundle formation –> membrane fusion
describe the capsid structure of HIV
T=20-23
216 hexamers
12 pentamers
where does reverse transcription in HIV occur? How are ATP and dNTP supplied?
RT occurs within virion
ATP and dNTP enter via pores
how many genome copies of HIV are in the capsid
two –> diploid virus
explain the mechanism of reverse transcription in HIV
HIV leader RNA has a dimerization sequence –> the two copies of genome interact via disulfide bridges at those sequence with another –> from kissing loop complex of one copy to extended duplex conformation if the sequences interact, the sequences are antiparallel to each other –> 3D structure important for reverse transcription –> template switching occurs between the two copies to prevent loss of information because nucleotides are cleaved of during integration into genome
Why does HIV have two genome copies?
ends are damaged during integration into host genome
What functions as primer in RT in HIV?
cellular tRNA Lys3
does Reverse transcriptase in HIV have proof reading function?
no –> error prone process
What are nucleotide reverse transcription inhibitors? And what do they lack?
they are nucleoside analogues that all lack 3’OH to halt polymerization
What are non-nucleoside RT inhibitors?
ATP like
what role does Nef play in HIV?
immune system:
- induces a singla cascade –> increased expression of NF-kB, AP-1 and NF_AT –> stimulation of gene expression in infected T-cells
- MHC I and II antigens reduced
what role does tat play in HIV infection?
- tat = trans activator of transcription
- binds to tar
- 100 fold increase of transcription by LTR promotor
- two exon product
- can induce apoptosis in uninfected by stander t cells if secreted to the blood
- hijacks host cell’s RNA pol II via interaction with P_TEFb
what role does Rev play in HIV infection?
- regulator of expression of virion proteins
- binds to RRE and is a posttrancriptional transactivator
–> timely regulation of gene expression - two exon product
what role does Vif play in HIV infection?
- hijacks cellular Cullin5 E3 ubiquitin ligase to target APOBE3G for degradation because APO is an innate defense factor against retro viruses
- vif coimmunoprecipitates with APOBEC3G
what role does vpu play in HIV infection?
- phosphorylated by casein kinase 2 increases the release of offspring in resting cells
- binds to CD4 receptor and induces ubiquitinilation and degradation of CD4
- prevents apoptosis (binds to TrCP)
what role does vpr play in HIV infection?
. binds to link protein p6
- accelerates viral infection
- works also as transactivator
- involved in transport of pre-integfration complex into nucleus (uses molecular mimicry of DNA)
- expression is rev dependent
what role does proteinase play in HIV infection?
- cleaves gag and gag-po, encoded polyproteins to produce functional components of the infectious virion
- aspartic protease (firemans grip)
- flap movement upon substrate binding or inhibition
what should an inhibitor mimic?
the transition state
what type of inhibitors can inhibit HIV?
- nucleoside reverse transcriptase inhibitors
- non nucleoside reverse transcriptase inhibitors
- protease inhibitors
- fusion inhibitors
what is ritonavir?
a protease inhibitor for HIV
what determines the outcome of evolution of protease mutanmt in the absence of drugs?
viral replication capacity
