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44 Cards in this Set
- Front
- Back
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Why is their co-copting of host cell ptns and machinery by the virus?
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Want to get:
Viral primo-infection Early steps in infection (uncoating, decapsidation) Reverse transcription complex, translocation Viral transcription, RNA export, RNA translation Transport of viral components (RNAs, ptns) Viral assembly (R, P and RNP transport) Viral morphogenesis, budding and maturation |
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What happens to the virus late in infection?
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RNA assembled into RNP granule
Transferred on cytoskeletal apparatus Moves along kinesin, which traffics things to the plasma mb |
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What happens to the virus early on in infection?
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Virus is incoming
Forms RNP RNP trafficked along mt to the Nucleus Use dynein motor to get into the nucleus |
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What does Gag interact with?
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Different cellular components
Can bind viral RNA, as well as motor ptns Can also interact with ICAM |
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What does HIV-1 Gag matrix influence on the host ptn?
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Influences HIV-1 RNA localization
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What part of Gag is important for genomic localization?
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N-terminal
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What happens if the N-term of Gag is mutated?
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Genomic RNA remains stuck in the nucleus
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What is Gag important for?
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Assembly and directing traffic of its own genome
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Where are the RNA trafficking sequences on Gag?
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Near the 5' UTR
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What viral ptn is important for the viral RNA movement out of the nucleus?
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Rev
(Rev binds the Rev response element (RRE)) |
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How do virus-host interactions influence RNA trafficking?
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Use A2RE-1/2, which are fctnal to mediate RNA transport from the nucleus to the cell cytoplasm
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What is hnRNP A2 for?
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Mediates RNA Export
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What happens if hnRNP is mutated?
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RNA remains in the nucleus (similar phenotype if you KO Rev)
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What happens if RNA trafficking/export is blocked?
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Get defective viral replication
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What happens if viral RNA is mutated so that it can no longer bind to hnRNP?
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Virus basically dies
Can't get out of nucleus |
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What is hRIP?
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Another host ptn that interacts with Rev
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What happens if a specific segment (33...) is removed from hRIP?
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RNA blocked in the nucleus
(similar to being Rev-negative) |
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What is absolutely essential to get HIV out of the nucleus?
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Rev + many other viral and host ptns ( viral gag, host eIF5A, hnRNP, hRIP etc)
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How does RNA travel on Mt?
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Travels down mt
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How can this travel be inhibited?
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Use different drugs:
Colcemid: depol Mt and block transport on MT Monensin: mb defects, accumulation of vesicles, vesicular budding, acidification of endosomal mbs -->Use these drugs and get localization of RNA on swollen endosomal mbs |
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What is required for MuMLV RNA to ride on the cellular vesicles?
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Dependence of RNA signals in retroviral RNA
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Why does MuMLV use recyling endosomal vesicles?
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To traffic their RNA genomes to the plasma mb and back
-->Virus uses natural trafficking material to get itself to the PM |
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What other virus is also trafficked on cellular vesicles?
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HIV-1
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What is dynein motor complex?
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Motor ptn that traffics cargo and viruses in a specific manner
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In which direction does dynein traffic ptns?
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Goes towards the (-) end
(Goes to the Nucleus) |
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Describe dynein motor fct
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Dynein is multisubunited and has a mt motor
Dynactin activates dynein and mediates mb binding Dynein/dynactin maintains golgi, endosomes and lysosomes in juxtanuclear position |
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What happens if dynamitin/p50 is overexpressed?
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Dynein doesn't work
Disrupt (-) end trafficking .: Everything will be stuck at the + end, near the PM |
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Does dynein fct influence HIV-1 RNA localization?
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Yes
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What happens if dynein is disrupted?
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Get co-trafficking of viral RNA with endosomal mbs
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What does RNA localization/trafficking depend on?
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1) Dynein motor activity
2) HIV-1 RNA cotrafficking on endosomes -->HIV-1 uses late endosomal vesicles to traffic its RNA |
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What is RILP?
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Rab7 interacting lysosomal ptn
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What does RILP do?
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Recruits dynein/dynactin late endosomes to the MTOC
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What happens if RILP is overexpressed?
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Similar to overexpressing dynamitin
Promote localization of late endosome/lysosome/nucleus -RNA is sequestered |
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What happens to viral and host ptns when RILP is overexpressed?
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Significant relocalization of genomic RNA, Gag and LAMP-1 at MTOC region (displaced during cell-cell transmission)
Since RNA is sequestered in MTOC, shows that MTOC is involved in trafficking |
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What happens if RILP is mutated?
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HIV-1 RNA disperses with late endosomal mbs
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What happens when virus infects a host?
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Traffic HIV-specific molec
When viral RNA is Tl, viral Gag is tethered to the vesicle by muristelation -->Recruits cellular ptns and RNAs -->Traffics along Mt, where virus wants to go -->Find dynein and kinesin on all endo mbs (they have opposing fcts) |
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What happens if the virus wants to get to the PM?
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Virus suppresses dynein and focuses on kinesin movement to the PM)
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When are Host and viral ptns critical to viral RNA and ptn translocation?
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During the early and late stage replication events
-->Thes ptns play critical roles in viral entry, gene expression and assembly and pathogenesis |
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Which viral ptn has a central role in most translocation event that occur early and late in the replication cycle?
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Gag
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What are cis-acting sequences bound by to mediate many steps in retroviral RNA movement, transport and trafficking (MA, hnRNP A2)?
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Viral and cellular trans-acting ptns
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How are retroviral genomic RNA and Gag trafficking mediated?
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On host vesicular trafficking machinery involving recycling and late endosomal vesicles)
-> Important role in viral assembly |
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When does the host molecular motor ptn KIF-4 bind retroviral Gags (MLV, HIV)?
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In outgoing virus particles and potentially mediates intracellular movement of RNP complexes
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What is motor ptn (dynein) used for?
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Translocation of outgoing and incoming particles
-->Trafficking on mt towards assembly sites |
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What are mt important for?
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Virus replication, to and from the MTOC
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