> Dissertation Defense Announcement
> To: The George Mason University Community
> Candidate: Weifeng Wang
> Program: PhD Biosciences*
> Date: Tuesday March 20, 2012
> Time: 1:30 p.m.
> Place: George Mason University
> Bull Run Hall, Room 258
> Prince William campus <http://www.gmu.edu/resources/visitors/findex.html>*
> *Dissertation Chair: Dr. Yuntao Wu
> Committee members: Dr. Daniel N. Cox, Dr. Barney Bishop, Dr. Weidong Zhou
> *Title: "A dichotomy in cortical actin and chemotactic actin activity between memory and na´ve T cells
> contributes to their differential susceptibility to HIV"
> *The dissertation is on reserve in the Johnson Center Library, Fairfax campus.
> The doctoral project will not be read at the meeting, but should be read in advance.
> All members of the George Mason University community are invited to attend.
> ABSTRACT:* *
> The persistence of viral reservoirs in HIV-infected patients impedes
> an effective cure to AIDS. One of the major viral reservoirs in the
> body is a small pool of latently infected CD45RO memory CD4 T cells.
> Human memory and na´ve CD4 T cells can be identified by the reciprocal
> expression of the CD45RO or CD45RA isoforms. In infected patients,
> CD45RO memory CD4 T cells are preferentially infected and harbor more
> integrated proviral DNA than CD45RA na´ve T cells. The molecular
> mechanism dictating this differential susceptibility to HIV-1 remained
> unknown. We discovered a phenotypic distinction between human memory
> (CD45RO+) and na´ve (CD45RA+) resting CD4 T cells in their cortical
> actin. Memory CD4+ T cells possess a higher cortical actin density and
> can be distinguished as CD45RO+ Actinhigh, in contrast, naive T cells
> are phenotypically CD45RA+Actinlow. In addition, we discovered that
> human memory CD4+ T cells possess a lower threshold for initiating
> signaling from CXCR4 than na´ve T cells. Low concentrations of
> chemokine SDF-1, the natural ligand to CXCR4, predominantly induce
> actin polymerization in memory CD4+ T cells. Furthermore, the binding
> of HIV envelope protein gp120 to CXCR4 triggers a strong signal
> transduction, which induces actin dynamics in memory but not na´ve
> CD4+ T cells. The dynamic actin cytoskeleton in memory CD4+ T cell
> promotes HIV reverse transcription and nuclei migration, which
> facilitates to the establishment of HIV latent reservoir. We further
> demonstrate that transient induction of actin dynamics by actin
> modulator in resting na´ve T cells rescues HIV latent infection. These
> results suggest a key role of chemotactic actin activity in
> facilitating HIV-1 latent infection of these T cell subsets.