[log in to unmask]" type="cite">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
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 naïve 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.


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 naïve 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 naïve T cells. The molecular mechanism dictating this differential susceptibility to HIV-1 remained unknown. We discovered a phenotypic distinction between human memory (CD45RO+) and naïve (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 naïve 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 naïve 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 naïve 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.