Herpesviruses establish a life-long infection in their hosts. This chronic infection at the host level is comprised of both lytic (productive) and latent (quiescent) phases. Lytic replication leads to infectious particle production and is essential for dissemination and transmission. Latency is characterized by the maintenance of the viral genome with a restricted gene expression program in long-lived host cells. The latent program of gammaherpesviruses Epstein-Barr Virus (EBV) and Kaposi’s sarcoma associated-herpesvirus (KSHV) in cellular reservoirs is associated with lymphomas and neoplasms. My research interests lie in understanding the molecular determinants of virus-host interactions during chronic gammaherpesvirus infections.
Murine gammaherpesvirus 68 (MHV68) is a natural pathogen of mice. MHV68 has genetic colinearity and biological parallels with its human counterparts. The ease of generating recombinant MHV68 viruses coupled with the availability of genetically altered mice provides a tractable model system to identify and characterize virus and host determinants of chronic infection. In addition, we can further define the molecular mechanisms of these determinants in lytic and latent cell culture systems.
The current focus of my lab is to understand the role of Nuclear Factor-kappa B (NF-kB) signaling during MHV68 infection. NF-κB transcription factors are activated by EBV and KSHV oncoproteins. NF-κB activation is critical for the efficient establishment and maintenance of a latent MHV68 infection in B lymphocytes. We are mapping the pathways that drive NF-κB activation during infection and evaluating the consequence of that activation for the cell and the virus. Another project is focused on identifying novel viral regulators of the NF-κB signaling pathway during lytic and latent infection. In addition, we aim to further define the role of NF-κB activation in particular cell-types and tissues in vivo.