>> Dissertation Defense Reminder
>> 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 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.
>>
>>
>> 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 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.
>>
>> ###
>>