Victor DeFilippis, Ph.D.
Research in Dr. DeFilippis’ laboratory focuses on the biology of virus-host interactions especially with regard to innate immune and inflammatory responses to infection. In particular, he is interested in 1) The cellular recognition of virus-associated molecules that triggers cellular synthesis and secretion of antiviral and proinflammatory cytokines; 2) The evasion of innate antiviral activity by viruses; and 3) Therapeutic manipulation of innate and inflammatory responses to block virus replication and enhance vaccine immunogenicity. The laboratory employs traditional techniques of cellular and molecular biology and animal models as well as the tools of systems biology and functional genomics. Specific foci of inquiry include the following:
1) Discovery and characterization of novel immunostimulatory compounds
The host innate immune response can be highly effective in both preventing replication of phylogenetically diverse viral pathogens but also in enhancing the initiation and establishment of adaptive immune responses. In light of this we employ high throughput screening strategies to identify novel small molecules capable of triggering specifically defined innate cellular signaling pathways and associated phenotypes. Ultimately the purpose of this research is to discover, characterize, and develop therapeutic compounds that can be used to both inhibit the spread of novel and other viral diseases as well as enhance the immunogenicity of vaccines.
2) Antiviral responses to Chikungunya virus
Chikungunya virus (CHIKV) is an RNA virus that is transmitted by mosquitoes and associated with the development of severe and persistent arthritis. In recent years CHIKV has experienced an explosive reemergence that has now entered the mainland United States. Unfortunately, comparatively little is known regarding the molecular biology of CHIKV-host cell interactions. Our work involves both characterization of the host pathogen-sensing apparatus involved in CHIKV detection and the cellular physiological state triggered by CHIKV infection as well as identification of strategies to block virus replication. This research employs cellular and transgenic murine models of CHIKV infection, immunity, and pathogenesis and relies on techniques such as RNA interference (in vitro and in vivo), directed viral mutation and ectopic gene insertion, proteomics, and transcriptomics.
3) Induction and evasion of innate immune responses by primate cytomegaloviruses
Human cytomegalovirus (HCMV) is a member of the herpesvirus family that infects human hosts persistently and is responsible for disease in numerous tissue types especially in immunocompromised patients. HCMV is also the leading infectious cause of birth defects. Exposure of human cells to HCMV triggers strong innate immune responses that include secretion of type I interferon and proinflammatory cytokines such as interleukin 1 β (IL-1β). We are focused on characterizing the cellular receptors and pathways triggered by cytomegalovirus infection that lead to induction of these innate responses. We are also investigating the immunostimulatory virus-associated molecules (nucleic acids, proteins) that are detected by infected cells that stimulate these pathways. This work involves microarray and quantitative PCR based analysis of virus-induced gene expression, RNA interference-mediated gene expression knockdown, lentivirus-dependent stable cell line construction, and promoter activation analysis using reporter cells.
Victor DeFilippis is an assistant scientist at the Vaccine and Gene Therapy Institute. After receiving his bachelor's degree from the University of Montana he received a Master's degree in Biology from Wayne State University. He completed his Ph.D. examining virus evolution at the University of California, Irvine. He conducted his postdoctoral work at the Vaccine and Gene Therapy Institute of OHSU.
Malouli D, Hansen SG, Nakayasu ES, Marshall EE, Hughes CM, Ventura AB, Gilbride RM, Lewis MS, Xu G, Kreklywich C, Whizin N, Fischer M, Legasse AW, Viswanathan K, Siess D, Camp DG 2nd, Axthelm MK, Kahl C, DeFilippis VR, Smith RD, Streblow DN, Picker LJ, Früh K. Cytomegalovirus pp65 limits dissemination but is dispensable for persistence. J Clin Invest. 2014 May 1;124(5):1928-44. [PMID: 24691437, PMCID: PMC4002596] Epub 2014 Apr 1.
Amsler L, Verweij MC, DeFilippis VR. The tiers and dimensions of evasion of the type I interferon response by human cytomegalovirus. J Mol Biol. 2013 Dec 13;425(24):4857-71. (doi: 10.1016/j.jmb.2013.08.023.) [PMID: 24013068, PMCID: PMC3864659] Epub 2013 Sep 5.
Messaoudi I, Vomaske J, Totonchy T, Kreklywich CN, Haberthur K, Springgay L, Brien JD, Diamond MS, Defilippis VR, Streblow DN. Chikungunya virus infection results in higher and persistent viral replication in aged rhesus macaques due to defects in anti-viral immunity. PLoS Negl Trop Dis. 2013 Jul 25;7(7):e2343. doi: 10.1371/journal.pntd.0002343. [PMID: 23936572, PMCID: PMC3723534]Print 2013.
Amsler L, Malouli D, DeFilippis V. The inflammasome as a target of modulation by DNA viruses. Future Virol. 2013 Apr 1;8(4):357-370. [PMID: 24955107, PMCID: PMC4061697]