April 2015


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"Diane St. Germain" <[log in to unmask]>
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Diane St. Germain
Thu, 23 Apr 2015 16:53:49 +0000
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Thesis Defense Announcement
To:  The George Mason University Community

Candidate: Huizhi Liang

Program: M.S. in Biology

Date:   Thursday April 30, 2015

Time:   10:30 AM

Place:  George Mason University
             Prince<> William Campus
             Bull Run Hall, Room 130

Title: "Mutagenesis on HIV-1 gp120 V3 Loop to Determine Effects on gp120-Mediated CCR5 and CXCR4 Signal Transduction in Resting CD4 T-Cells"
Thesis Director: Dr. Yuntao Wu
Thesis Committee:  Dr. Ramin Hakami, Dr. Jia Guo
A copy of the thesis will be available in the Mercer Library.  All are invited to attend the defense.
The M-tropic HIV-1 viruses use CCR5 as the co-receptor for entry. The V3 loop in the M-tropic envelope protein, gp120, is largely responsible for the selection of the CCR5 co-receptor. Mutations in the V3 loop frequently lead to viral tropism switch to use CXCR4, which is associated with rapid disease progression. Recent studies from our laboratory have suggested that during viral entry, HIV-1 also triggers signal transduction through gp120 binding to CXCR4 on resting CD4 T cells. This signal transduction leads to actin dynamics, facilitating viral post entry steps. In this study, I examined the role of individual mutations in the V3 loop for viral tropism switch. We selected and mutated six amino acids in the V3 loop of the M-tropic YU2 gp120. Effects of these mutations on viral entry and viral tropism switch (R5- to X4-tropism) were analyzed. In addition, I also investigated whether these mutations alter gp120 signaling through CCR5 or CXCR4 in resting CD4 T cells. My results demonstrated that these mutations alter the ability of HIV-1 to trigger signal through CCR5, diminishing HIV infectivity. However, these mutations were not sufficient to confer viral tropism switch and the ability to trigger signal transduction through CXCR4.