Victor DeFilippis, Ph.D.

Biography
Dr. DeFilippis received his B.A. from the University of Montana and his Ph.D. in Biology from the University of California at Irvine where his research examined the molecular evolution and population genetics of viruses. He joined the VGTI in 2001 as a postdoctoral research fellow in the laboratory of Dr. Klaus Früh. He became a research assistant professor in 2005.

Research Overview
The main focus of my research is the host innate immune response to viral infection and the mechanisms employed by viruses to counteract, tolerate, or circumvent these reactions. I am particularly interested in the virus-mediated induction of interferon synthesis, the transcription and activity of interferon-stimulated antiviral genes, and the viral phenotypes that have arisen to withstand or inhibit these molecular responses. I am primarily using human and rhesus cytomegalovirus (CMV) as model systems for both in vitro and in vivo experiments.

1. Induction and evasion of interferon-stimulated genes by human and rhesus cytomegaloviruses. Despite their genomic similarities, human and rhesus CMV elicit radically different responses by host cells following infection. While human CMV strongly induces transcription of interferon and antiviral host genes, rhesus CMV fully suppresses this response. We are taking advantage of these disparities to understand and characterize the molecular bases of innate immune induction and inhibition by CMVs.

 

1. Examining the role of CMV tegument proteins in immune evasion in vivo. CMV virus particles possess a large amount of virally-encoded, virion-associated proteins of mostly unknown function. One of the most abundant phosphoproteins, pp65, is suspected to exhibit immunosuppressive properties during natural infection. By using pp65-deleted viruses we are characterizing and comparing the adaptive immune response to wild type versus mutant viruses to elucidate the role of these proteins in immunomodulation during infection.

Selected References
DeFilippis, V.R. Induction and evasion of type I interferon responses by cytomegaloviruses. Current Topics in Innate Immunity (in press).

Streblow, D. N., K. W. van Cleef, C. N. Kreklywich, C. Meyer, P. Smith, V.R. DeFilippis, F. Grey, K. Fruh, R. Searles, C. Bruggeman, C. Vink, J. A. Nelson, and S. L. Orloff. 2007. Rat Cytomegalovirus Gene Expression in Cardiac Allograft Recipients Is Tissue Specific and Does Not Parallel the Profiles Detected in Vitro. J. Virology 81: 3816-3826.

DeFilippis, V.R., B. Robinson, T. Keck, S.G. Hansen, J.A. Nelson and K.J. Früh. 2006. Interferon regulatory factor 3 is necessary for induction of antiviral genes during human cytomegalovirus infection. J. Virology 80: 1032-1037.

DeFilippis, V.R. and K.J. Früh. Host cell targets for antiviral therapy: An update. 2006. Future Virology 1:509-518

DeFilippis, V.R. and K.J. Früh. 2005. Inhibition of interferon regulatory factor 3 activation by rhesus cytomegalovirus virions. J. Virology 79:6419–6431.

Rue, C.A., M.A. Jarvis, A.J. Knoche, H.L. Meyers, V. R. DeFilippis, S.G. Hansen, M. Wagner, K.J. Früh, D.G. Anders, S.W. Wong, P.A. Barry, and J.A. Nelson. A Cyclooxygenase-2 Homologue Encoded by Rhesus Cytomegalovirus Is a Determinant for Endothelial Cell Tropism. J. Virology 2004 78: 12529-12536.

DeFilippis, V.R., C. Raggo, A.V. Moses, and K.J. Früh. 2003. Functional genomics in virology and antiviral drug discovery. Trends in Biotechnology 21:452-7.

DeFilippis, V.R. and L.P. Villarreal. 2001. Virus evolution. Chapter 13 in Fields Virology, edited by D.M. Knipe and P.M. Howley. Lippincott - Raven Publishers. Philadelphia.