Kulkarni, Anurag (2011) The role of VIF in overcoming the APOBEC3G block to HIV-1 replication. PhD thesis, University of Warwick.

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Abstract

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.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QR Microbiology
Library of Congress Subject Headings (LCSH):	HIV (Viruses)
Official Date:	April 2011
Dates:	Date Event April 2011 Submitted
Institution:	University of Warwick
Theses Department:	School of Life Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	McCrae, M.
Sponsors:	University of Warwick ; Overseas Research Students Awards Scheme (ORSAS)
Extent:	xxiii, 256 leaves : ill., charts
Language:	eng

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