Title: Unraveling the Mechanisms of Natural Killer Cell-Mediated Resistance to a Viral Disease

Presenter: Min Fang, Staff Scientist

University: Immune Cell Development and Host Defense, Fox Chase Cancer Center

Time: 10:30-11:30, 1 April, 2011

Venue: A102, Institute of Microbiology, Chinese Academy of Sciences

Abstract: Natural Killer (NK) cells are innate effector cells serving as a first line of defense against certain viral infections and tumors. To date, only a few NK cell receptor-ligand interactions important for resistance to viral diseases have been characterized. Ectromelia virus (ECTV) is an orthopoxvirus (OPV) that causes mousepox, the murine equivalent of human smallpox. C57BL/6 (B6) mice are naturally resistant to mousepox due to the concerted action of innate and adaptive immune responses. Previous studies have shown that NK cells are essential for the B6 mice resistance to mousepox, however, the mechanism of NK cell-mediated resistance were undefined. We have shown that B6 mice resistance to mousepox requires the direct cytolytic function of NK cells to control early virus dissemination, and the activating receptor NKG2D is required for optimal NK cell-mediated killing. Furthermore, we recently demonstrated that CD94, a molecule preferentially expressed by NK cells, is essential for the resistance of B6 mice to mousepox. CD94-NKG2E is the activating NK cell receptor recognizing ECTV infected cells and in a Qa-1b dependent manner. Together, our findings have important implication towards the understanding of natural resistance to pathogenic viral infections.