William B. Klimstra, PhD
8037 Biomedical Science Tower 3
3501 Fifth Avenue
Pittsburgh, PA 15213
The goal of my laboratory has been to define the host and viral factors that determine the success or failure of the innate immune response to infection with arthropod-borne viruses. The specific approach is to examine at the single cell level, the molecular mechanisms that determine host cell permissivity to the alphaviruses (e.g., Sindbis virus [SB], Venezuelan equine encephalitis virus [VEEV], eastern equine encephalitis virus [EEEV], western equine encephalitis virus [WEEV], Chikungunya virus [CHIKV] and Ross River virus [RRV]) and the contribution of replication in specific cells to the pathogenesis of viral disease. Upon introduction into a susceptible host, alphaviruses initially replicate within cells of the dendritic cell (DC) and macrophage lineages. In young animals, this replication is unrestrained and leads to induction of a toxic proinflammatory cytokine response. However, in adults virus replication and cytokine induction are restricted by one or more as yet uncharacterized mechanisms. These mechanisms likely involve changes in host cell permissivity to virus infection. Ongoing studies include: determination of the relationship between infection of DC/macrophage and induction of the systemic inflammatory response, identification and characterization of cellular receptors that promote virus infection and identification of host innate immune mechanisms that control virus replication within individual cells. Furthermore, since the extent of virus replication, viral cellular tropism and the host response to infection are critical factors in stimulation of robust and appropriate immune responses to immunogens, we also strive to translate information gained from pathogenesis studies into strategies for improvement of alphavirus-based gene delivery systems.
Dr. Klimstra conducts his research through the Center for Vaccine Research. Learn more>