Photo of Jay A. Nelson, Ph.D.

Jay A. Nelson Ph.D.

  • (503) 418-2710
    • Professor VGTI-Vaccine and Gene Therapy Institute
    • Molecular Microbiology and Immunology Graduate Program School of Medicine
    • Program in Molecular and Cellular Biosciences School of Medicine

The long-term goal of Dr. Nelson’s research is to understand the molecular basis of disease mediated by pathogenic human viruses. A major focus in the laboratory has been the identification of mechanisms involved in the pathogenesis of cytomegalovirus (CMV). CMV is a ubiquitous opportunistic infection that is usually asymptomatic following infection in the host. However, in immunocompromised individuals, CMV can cause significant disease. The topics that we are currently pursuing in the laboratory are as follows: 1) molecular mechanisms of CMV latency, persistence, and reactivation in macrophages and endothelial cells; 2) establishment of a mouse model to examine mechanisms of HCMV latency and reactivation 3) characterization of the function of CMV-encoded miRNAs in the replication cycle of the virus; 4) analysis and function of CMV induced secreted extracellular proteins (secretome) in the induction of wound healing and angiogenesis that may be related to viral acceleration of vascular disease;  5) mechanisms of CMV assembly and glycoprotein trafficking 6) analysis of the CMV proteome; and  7) the use of recombinant CMV as a vaccine vector for SIV/HIV and monkeypox.Another focus of the laboratory has been elucidation of West Nile virus (WNV) replication and pathogenesis. In collaboration with the Frueh laboratory using microarray analysis of up and down-regulated cellular genes, we observed that WNV significantly up-regulated the cellular Src kinase cYes. Inhibition of c-Yes production by siRNA or activity by the SFK inhibitor PP2 resulted in a significant drop in viral production (5-6 logs) in WNV infected cells. We have observed that cYes is involved in the maturation of the virion glycoprotein preventing viral egress from the ER. These observations will allow us to explore mechanisms of flavivirus assembly and egress as well as identify potential targets for therapeutic intervention. We have also observed that WNV sequesters cYes from cellular tight junctions perturbing barrier function that may be related to CNS disease observed in infected animals.

Areas of interest

  • Flaviviruses
  • CMV Pathogenesis
  • West Nile Virus
  • HIV Virology and Pathobiology

Education

  • Ph.D., Oregon State University, Corvalis Oregon 1980

Memberships and associations

  • Fellow, American Academy of MicrobiologyAmerican Cancer Society American Society of VirologyAmerican Association for the Advancement of Science

Publications

Selected publications

  • Hirsch AJ, Smith JL, Haese NN, Broeckel RM, Parkins CJ,Kreklywich C, DeFilippis VR, Denton M, Smith PP, Messer WB, Colgin LM, DucoreRM, Grigsby PL, Hennebold JD, Swanson T, Legasse AW, Axthelm MK, MacAllister R,Wiley CA, Nelson JA, Streblow DN. Zika Virus infection of rhesus macaques leadsto viral persistence in multiple tissues.        
    PLoS Pathog. 2017 Mar9;13(3):e1006219. doi: 10.1371/journal.ppat.1006219. PMID: 28278237, PMC5381941

  • Hancock MH, Hook LM, Mitchell J, Nelson JA; Human Cytomegalovirus MicroRNAs miR-US5-1 and miR-UL112-3p Block Pro inflammatory Cytokine Production in Response to NF-κB-Activating Factors through Direct Down regulation of IKKα and IKKβ. MBio. 2017 Mar 7;8(2). pii: e00109-17. doi:10.1128/mBio.00109-17. PMID: 28270578, PMC5340867

  • Burwitz BJ, Malouli D, Bimber BN, Reed JS, Ventura AB,Hancock MH, Uebelhoer LS, Bhusari A, Hammond KB, Espinosa Trethewy RG, Klug A,Legasse AW, Axthelm MK, Nelson JA, Park BS, Streblow DN, Hansen SG, Picker LJ,Früh K, Sacha JB. Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques. PLoS Pathog. 2016 Nov 9;12(11):e1006014. doi:10.1371/journal.ppat.1006014. PMID: 27829026, PMCID: PMC5102353

  • Caviness K, Bughio F, Crawford LB, Streblow DN, Nelson JA,Caposio P, Goodrum F. Complex Interplay of the UL136 Isoforms BalancesCytomegalovirus Replication and Latency. MBio. 2016 Mar 1;7(2):e01986. doi:10.1128/mBio.01986-15. PMID: 26933055, PMCID: PMC4810493

  • Hansen SG, Wu HL, Burwitz BJ, Hughes CM, Hammond KB, VenturaAB, Reed JS, Gilbride RM, Ainslie E, Morrow DW, Ford JC, Selseth AN, Pathak R,Malouli D, Legasse AW, Axthelm MK, Nelson JA, Gillespie GM, Walters LC,Brackenridge S, Sharpe HR, López CA, Früh K, Korber BT, McMichael AJ,Gnanakaran S, Sacha JB, Picker LJ. Broadly targeted CD8? T cell responsesrestricted by major histocompatibility complex E. Science. 2016 Feb12;351(6274):714-20. doi: 10.1126/science.aac9475. PMID: 26797147, PMCID: PMC4769032

Publications

  • "Evasion of CD8+ T Cells Is Critical for Superinfection by Cytomegalovirus" Science April 2 2010
  • "Human Cytomegalovirus miR-UL112-3p Targets TLR2 and Modulates the TLR2/IRAK1/NFκB Signaling Pathway" PLoS Pathogens May 1 2015
  • "Direct interaction of the human cytomegalovirus IE86 protein with the cis repression signal does not preclude TBP from binding to the TATA box" Journal of Virology September 1993
  • "Optimal conditions for detection of reverse transcriptase activity in human placentas" Biochimica et Biophysica Acta - Gene Structure and Expression September 10 1984
  • "Rat cytomegalovirus-accelerated transplant vascular sclerosis is reduced with mutation of the chemokine-receptor R33" American Journal of Transplantation March 2005
  • "FAK promotes organization of fibronectin matrix and fibrillar adhesions" Journal of Cell Science January 15 2004
  • "Interactions between cytomegalovirus immediate-early proteins and the long terminal repeat of human immunodeficiency virus" Reviews in Medical Virology  1993
  • "Isolation and characterization of a low-abundance splice variant from the human cytomegalovirus major immediate-early gene region" Journal of Virology  1995
  • "Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms" Science  2013
  • "Coding potential of laboratory and clinical strains of human cytomegalovirus" Proceedings of the National Academy of Sciences of the United States of America December 9 2003
  • "West nile virus capsid degradation of claudin proteins disrupts epithelial barrier function" Journal of Virology June 2009
  • "Characterization of the human cytomegalovirus gH/gL/UL128-131 complex that mediates entry into epithelial and endothelial cells" Journal of Virology January 2008
  • "Transformation of NIH 3T3 cells with cloned fragments of human cytomegalovirus strain AD169" Journal of Virology  1982
  • "Identification and function of human cytomegalovirus microRNAs" Journal of Clinical Virology March 2008
  • "Human cytomegalovirus secretome contains factors that induce angiogenesis and wound healing" Journal of Virology July 2008
  • "The enhancer domain of the human cytomegalovirus major immediate-early promoter determines cell type-specific expression in transgenic mice" Journal of Virology  1996
  • "An isoform variant of the cytomegalovirus immediate-early auto repressor functions as a transcriptional activator" Virology  1992
  • "T cell recognition of HIV synthetic peptides in a natural infection" Journal of Immunology  1989
  • "Promoter-specific trans activation and repression by human cytomegalovirus immediate-early proteins involves common and unique protein domains" Journal of Virology  1990
  • "HSV, CMV, and HPV in human neoplasia" Journal of Investigative Dermatology  1984
  • "Identification and potential function of viral microRNAs"  January 1 2007
  • "Human immunodeficiency virus (HIV) and JC virus in acquired immune deficiency syndrome (AIDS) patients with progressive multifocal leukoencephalopathy" Acta Neuropathologica July 1988
  • "Flaviviruses are sensitive to inhibition of thymidine synthesis pathways" Journal of Virology  2013
  • "HIV infection of the brain microvasculature and its contribution to the AIDS dementia complex" Journal of Neuro-AIDS  1996
  • "Humanized mouse models of human cytomegalovirus infection" Current Opinion in Virology June 29 2015
  • "West Nile virus entry requires cholesterol-rich membrane microdomains and is independent of αvβ3 integrin" Journal of Virology June 2008
  • "Biologic and molecular properties of the AIDS-associated retrovirus that affect antiviral therapy" Annales de l'Institut Pasteur Virology  1987
  • "Diagnosis of AIDS by using a 12-amino acid peptide representing an immunodominant epitope of the human immunodeficiency virus" Journal of Infectious Diseases  1987
  • "Sequences regulating tropism of human immunodeficiency virus type 1 for brain capillary endothelial cells map to a unique region on the viral genome" Journal of Virology  1996
  • "Pathogenesis of HIV encephalitis" Pathology International  1991

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