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

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

  • "Human cytomegalovirus induces cellular and humoral virus-specific immune responses in humanized BLT mice." Scientific Reports  In: , Vol. 7, No. 1, 937, 01.12.2017.
  • "Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues." PLoS Pathogens In: , Vol. 13, No. 3, e1006219, 01.03.2017.
  • "Human cytomegalovirus microRNAs miR-US5-1 and miR-UL112-3p block proinflammatory cytokine production in response to NF-κB-activating factors through direct downregulation of IKKα and IKKβ." mBio In: , Vol. 8, No. 2, e00109-17, 01.03.2017.
  • "Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques." PLoS Pathogens In: , Vol. 12, No. 11, e1006014, 01.11.2016.
  • "Complex interplay of the UL136 isoforms balances cytomegalovirus replication and Latency." mBio  In: , Vol. 7, No. 2, e01986-15, 01.03.2016.
  • "Broadly targeted CD8 T cell responses restricted by major histocompatibility complex E." Science In: , Vol. 351, No. 6274, 12.02.2016, p. 714-720.
  • "Humanized mouse models of human cytomegalovirus infection." Current Opinion in Virology  In: , Vol. 13, 29.06.2015, p. 86-92.
  • "Human Cytomegalovirus miR-UL112-3p Targets TLR2 and Modulates the TLR2/IRAK1/NFκB Signaling Pathway." PLoS Pathogens In: , Vol. 11, No. 5, e1004881, 01.05.2015.
  • "Erratum : Immune clearance of highly pathogenic SIV infection (Nature (2013) 502 (100-104) DOI:10.1038/nature12519))." Nature In: , Vol. 514, No. 7524, 30.10.2014, p. 654.
  • "Human cytomegalovirus-encoded pUL7 is a novel CEACAM1-like molecule responsible for promotion of angiogenesis." mBio  In: , Vol. 5, No. 6, e02035-14, 26.09.2014.
  • "Cytomegalovirus miRNAs target secretory pathway genes to facilitate formation of the virion assembly compartment and reduce cytokine secretion." Cell Host and Microbe In: , Vol. 15, No. 3, 12.03.2014, p. 363-373.
  • "Transcriptome-wide discovery of microRNA binding sites in Human Brain." Neuron In: , Vol. 81, No. 2, 22.01.2014, p. 294-305.
  • "HCMV Infection of Humanized Mice after Transplantation of G-CSF-Mobilized Peripheral Blood Stem Cells from HCMV-Seropositive Donors." Biology of Blood and Marrow Transplantation In: , Vol. 20, No. 1, 01.2014, p. 132-135.
  • "Cytomegalovirus microRNAs." Current Opinion in Virology In: , Vol. 7, No. 1, 2014, p. 40-46.
  • "Techniques for characterizing cytomegalovirus-encoded miRNAs." Methods in Molecular Biology In: , Vol. 1119, 2014, p. 239-265.
  • "Inhibition of dengue virus replication by a class of small-molecule compounds that antagonize dopamine receptor d4 and downstream mitogen-activated protein kinase signaling." Journal of Virology In: , Vol. 88, No. 10, 2014, p. 5533-5542.
  • "Human cytomegalovirus-encoded pUL7 is a novel CEACAM1-like molecule responsible for promotion of angiogenesis." mBio  In: , Vol. 5, No. 6, 2014, p. e02035.
  • "Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms." Science In: , Vol. 340, No. 6135, 1237874, 2013.
  • "Flaviviruses are sensitive to inhibition of thymidine synthesis pathways." Journal of Virology  In: , Vol. 87, No. 17, 2013, p. 9411-9419.
  • "Functional genomics approaches to understand cytomegalovirus replication, latency and pathogenesis." Current Opinion in Virology In: , Vol. 3, No. 4, 2013, p. 408-415.
  • "Immune clearance of highly pathogenic SIV infection." Nature In: , Vol. 502, No. 7469, 2013, p. 100-104.
  • "Rhesus cytomegalovirus encodes seventeen microRNAs that are differentially expressed in vitro and in vivo." Virology In: , Vol. 425, No. 2, 10.04.2012, p. 133-142.
  • "A novel human cytomegalovirus locus modulates cell type-specific outcomes of infection." PLoS Pathogens  In: , Vol. 7, No. 12, e1002444, 12.2011.
  • "Human cytomegalovirus US7 is regulated synergistically by two virally encoded microRNAs and by two distinct mechanisms." Journal of Virology  In: , Vol. 85, No. 22, 11.2011, p. 11938-11944.
  • "BST2/tetherin enhances entry of human cytomegalovirus." PLoS Pathogens  In: , Vol. 7, No. 11, e1002332, 11.2011.
  • "Inhibition of dengue virus infections in cell cultures and in AG129 mice by a small interfering RNA targeting a highly conserved sequence." Journal of Virology  In: , Vol. 85, No. 19, 10.2011, p. 10154-10166.
  • "Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine." Nature In: , Vol. 473, No. 7348, 26.05.2011, p. 523-527.
  • "High-content assay to identify inhibitors of dengue virus infection." Assay and Drug Development Technologies  In: , Vol. 8, No. 5, 01.10.2010, p. 553-570.
  • "Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model." Cell Host and Microbe In: , Vol. 8, No. 3, 16.09.2010, p. 284-291.
  • "A viral microRNA down-regulates multiple cell cycle genes through mRNA 59′UTRs." PLoS Pathogens In: , Vol. 6, No. 6, 06.2010.

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