The Department of Microbiology and Immunology is pleased to announce that Sean Gregory, a graduate student in Blossom Damania’s lab, is the 2011 G. Philip Manire Graduate Student Excellence in Research Award recipient. Sean has shown outstanding scientific accomplishments through his studies of a mechanism of KSHV latency reactivation and a strategy for viral inhibition of the inflammasome. In a 2009 PNAS paper, Sean described how exposure of latently infected PEL cells to TLR7/8 agonists (single stranded RNA or VSV infection) resulted in reactivation of KSHV. While this finding may impact modalities for controlling KSHV pathogenesis, it also reveals an instance of complex interplay between the host innate immune response and heterologous viruses in the context of latent infection. In his 2011 Science paper, Sean described the first example of a pathogen-encoded protein that could inhibit the NLRP1 inflammasome. Specifically, KSHV Orf63 protein blocked NLRP1 self-association, caspase-1 activation, and processing of IL-1 beta and IL-18.
His demonstration that knockdown of ORF63 resulted in less efficient virus reactivation and replication, will likely spur the search for similar pathogen-encoded inflammasome antagonists. This work also underscores the importance of subverting the inflammasome for long-term host pathogen interactions.
This Manire award, for the most significant and impressive research project by a graduate student, is given in memory of Dr. Manire, recognizing his dedication to the University of North Carolina and to the Department of Microbiology & Immunology, as well as his love of graduate education and research.