This project focuses on the Virus Infectivity Factor protein of HIV-1 and its relief of the block to virus replication exerted by the APOBEC3G component of the innate immune response. Virus Infectivity Factor (vif) is an accessory gene of HIV, deletion of which leads to large drops in virus infectivity. This decrease in infectivity was found to be due to APOBEC3G, an inhibitor of HIV replication which is constitutively expressed in peripheral blood mononuclear cells (PBMCs), the natural host cells for HIV in humans. Vif is indispensable to block the inhibitory effects of APOBEC3G thereby allowing normal viral replication to continue inside the host. This recognition of the critical role played by Vif in the viral replication cycle has centred studies on characterising the interactions of Vif with both APOBEC3G as well as other virus encoded proteins. Stimulation of proteasomal degradation of APOBEC3G is currently believed to be the primary anti-APOBEC3G effect induced by Vif. However recent reports, particularly those showing that Vif remains able to block the inhibitory actions of degradation resistant APOBEC3G, question the validity of this hypothesis. The recognition that both APOBEC3G and Vif become incorporated into HIV particles through an interaction with the precursor of the virion structural proteins, Pr55GAG has raised the possibility that they may compete with each other for this incorporation. Using techniques such as mammalian two-hybrid assays, sucrose gradient analysis of GAG virus-like particles (VLPs) and confocal imaging, the interactions of these proteins with Pr55GAG have been analyzed and the results obtained indicate that Vif competes with APOBEC3G for Pr55GAG binding leading to its displacement and exclusion from the budding HIV virions. This potentially important pathway for Vif activity and its significance in the development of novel antiretroviral drugs in the future will be discussed.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:537752 |
| Date | January 2011 |
| Creators | Kulkarni, Anurag |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/36847/ |
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