My research interests involve studying the interactions between viruses and the innate immune response, specifically natural killer (NK) cells, in an effort to develop new preventive strategies for human viral infections.
NK cells are large granular lymphocytes that play a central role in the control of viral infections. NK cells recognize and kill virus-infected cells during the early stages of the infection, prior to the development of adaptive immunity. Elimination of these infected target cells is mediated by a number of different mechanisms, including:
1. Exocytosis of cytoplasmic granules containing perforin and granzyme
2. Fas ligand–mediated induction of apoptosis
3. Antibody-dependent cellular cytotoxicity (ADCC)
NK cells are important to the innate immune response against several viral infections including: cytomegalovirus (CMV), influenza virus, hepatitis C virus (HCV), and human immuno-deficiency virus-1 (HIV-1).
We have created a genetic murine model which lack expression of the Ly49 receptor family. This allows us to study the role of these receptors on NK cells in the control of various viral infections, in particular influenza virus and CMV.
Using Ly49-deficient mice, we show that influenza virus infection has a propensity to up-regulate cell surface expression of MHC-I, a ligand for the inhibitory Ly49 receptor, on infected lung epithelial cells. As a result, Ly49-deficient mice exhibit better survival and significantly lower viral load than wild-type mice when infected with influenza virus. Accordingly, blocking of the Ly49:MHC-I interaction is protective against influenza virus infection.