The long-term goal of the Wong laboratory is to understand how viruses cause disease. This is important and essential for developing effective antiviral therapies and potential vaccines to prevent infection or disease progression. The Wong lab is currently investigating simian gamma-herpesviruses, which induce disease similar to human gamma-herpesviruses, which cause severe and chronic disease in humans. Human herpesviruses, are very specific for their natural hosts, a factor that complicates the ability to study the pathogenic mechanisms of the human viruses in an animal model. An alternative approach is to utilize animal models that harbor viruses that are closely related to the human virus. One animal model that has proven to be invaluable in understanding the mechanisms of infectious disease and for vaccine development is the nonhuman primate. Dr. Wong is investigating two gamma-herpesviruses: one that is associated with an immune-mediated disease that closely possesses clinical, immunopathological and histopathological features to multiple sclerosis; and a second gamma-herpesvirus that is associated with lymphoproliferative disorder in the context of acquired immunodeficiency, a disease manifestation that closely parallels disease in AIDS patients caused by Kaposi sarcoma-associated herpesvirus.

By employing molecular, genetic and virological techniques, members of Dr. Wong’s laboratory examine how these nonhuman primate viruses infect and replicate in cell culture and eventually how they cause illnesses in vivo. They have shown that experimental inoculation of immunocompromised monkeys with simian herpesviruses results in disease manifestations that closely resemble those observed in humans infected with the human immunodeficiency virus (HIV). Utilizing these approaches, they are identifying the viral determinants that contribute to disease and are devising novel recombinant molecules to help prevent viral pathogenesis.

Biography

Dr. Wong received his Ph.D. from Stanford University School of Medicine in 1987 studying the process of eukaryotic DNA replication. Upon completing his doctorate, he performed post-doctoral research at Harvard Medical School, where he focused on human herpesvirus replication and pathogenesis. He came to the Oregon Regional Primate Research Center in 1991 as an Assistant Scientist in the Division of Pathobiology and Immunology, and is now a Professor in the Vaccine and Gene Therapy Institute. Dr. Wong has joint appointments with the Division of Pathobiology and Immunology at the Oregon National Primate Research Center and in the Department of Molecular Microbiology and Immunology in the OHSU School of Medicine.

Publications

• Springgay LK, Fitzpatrick K, Park B, Estep RD, Wong SW. Rhesus Macaque Rhadinovirus Encodes a Viral Interferon Regulatory Factor To Disrupt Promyelocytic Leukemia Nuclear Bodies and Antagonize Type I Interferon Signaling. J Virol. 2019 Mar 5;93(6). pii: e02147-18. doi: 10.1128/JVI.02147-18. Print 2019 Mar 15.
• Marshall VA, Labo N, Hao XP, Holdridge B, Thompson M, Miley W, Brands C, Coalter V, Kiser R, Anver M, Golubeva Y, Warner A, Jaffe ES, Piatak M Jr, Wong SW, Ohlen C, MacAllister R, Smedley J, Deleage C, Del Prete GQ, Lifson JD, Estes JD, Whitby D. Gammaherpesvirus infection and malignant disease in rhesus macaques experimentally infected with SIV or SHIV. PLoS Pathog. 2018 Jul 12;14(7):e1007130. doi: 10.1371/journal.ppat.1007130. eCollection 2018 Jul. [PMID: 30001436]
• Estes JD, Wong SW, Brenchley JM. Nonhuman primate models of human viral infections. Nat Rev Immunol. 2018 Jun;18(6):390-404. doi: 10.1038/s41577-018-0005-7. [PMID: 29556017]
• Skalsky RL, Barr SA, Jeffery AJ, Blair T, Estep R, Wong SW. JapaneseMacaque Rhadinovirus Encodes a Viral MicroRNA Mimic of the miR-17 Family. JVirol. 2016 Sep 29;90(20):9350-63. doi: 10.1128/JVI.01123-16. [PMID: 27512057]
• Blair TC, Manoharan M, Rawlings-Rhea SD, Tagge I, Kohama SG,Hollister-Smith J, Ferguson B, Woltjer RL, Frederick MC, Pollaro J, Rooney WD,Sherman LS, Bourdette DN, Wong SW. Immunopathology of Japanese macaqueencephalomyelitis is similar to multiple sclerosis. J Neuroimmunol. 2016 Feb15;291:1-10. doi: 10.1016/j.jneuroim.2015.11.026. [PMID: 26857488]
• Morin G, Robinson BA, Rogers KS, Wong SW.;A RhesusRhadinovirus Viral Interferon (IFN) Regulatory Factor Is Virion Associated andInhibits the Early IFN Antiviral Response. J Virol. 2015 Aug;89(15):7707-21.doi: 10.1128/JVI.01175-15.[PMID: 25972548]
• Franceschi V, Parker S, Jacca S, Crump RW, Doronin K,Hembrador E, Pompilio D, Tebaldi G, Estep RD, Wong SW, Buller MR, Donofrio G.;BoHV-4-BasedVector Single Heterologous Antigen Delivery Protects STAT1(-/-) Mice fromMonkeypoxvirus Lethal Challenge. PLoS Negl Trop Dis. 2015 Jun 18;9(6):e0003850.doi: 10.1371/journal.pntd.0003850.[PMID: 26086739]
• Vatter HA, Donaldson EF, Huynh J, Rawlings S, Manoharan M, Legasse A, Planer S, Dickerson MF, Lewis AD, Colgin LM, Axthelm MK, Pecotte JK, Baric RS, Wong SW, Brinton MA. A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques. Virology. 2015 Jan 1;474:186-98. (doi: 10.1016/j.virol.2014.10.018.) [PMID: 25463617] Epub 2014 Nov 19.
• Estep RD, Rawlings SD, Li H, Manoharan M, Blaine ET, O'Connor MA, Messaoudi I, Axthelm MK, Wong SW. The rhesus rhadinovirus CD200 homologue affects immune responses and viral loads during in vivo infection. J Virol. 2014 Sep;88(18):10635-54. (doi: 10.1128/JVI.01276-14.) [PMID: 24991004, PMCID: PMC4178886] Epub 2014 Jul 2.
• Alzhanova D, Hammarlund E, Reed J, Meermeier E, Rawlings S, Ray CA, Edwards DM, Bimber B, Legasse A, Planer S, Sprague J, Axthelm MK, Pickup DJ, Lewinsohn DM, Gold MC, Wong SW, Sacha JB, Slifka MK, Früh K. T cell inactivation by poxviral B22 family proteins increases viral virulence. PLoS Pathog. 2014 May 15;10(5):e1004123. (doi: 10.1371/journal.ppat.1004123.) [PMID: 24832205, PMCID: PMC4022744] eCollection 2014.
• Estep RD, Wong SW. Rhesus macaque rhadinovirus-associated disease. Curr Opin Virol. 2013 Jun;3(3):245-50. (doi: 10.1016/j.coviro.2013.05.016.) [PMID: 23747119, PMCID: PMC3780577] Epub 2013 Jun 6.
• Estep RD, Hansen SG, Rogers KS, Axthelm MK, Wong SW. Genomic characterization of Japanese macaque rhadinovirus, a novel herpesvirus isolated from a nonhuman primate with a spontaneous inflammatory demyelinating disease. J Virol. 2013 Jan;87(1):512-23. (doi: 10.1128/JVI.02194-12.) [PMID: 23097433, PMCID: PMC3536378] Epub 2012 Oct 24.
  Robinson BA, O'Connor MA, Li H, Engelmann F, Poland B, Grant R, DeFilippis V, Estep RD, Axthelm MK, Messaoudi I, Wong SW. Viral interferon regulatory factors are critical for delay of the host immune response against rhesus macaque rhadinovirus infection. J Virol. 2012 Mar;86(5):2769-79. (doi: 10.1128/JVI.05657-11.) [PMID: 22171275, PMCID: PMC3302252] Epub 2011 Dec 14.
• Robinson BA, Estep RD, Messaoudi I, Rogers KS, Wong SW. Viral interferon regulatory factors decrease the induction of type I and type II interferon during rhesus macaque rhadinovirus infection. J Virol. 2012 Feb;86(4):2197-211. (doi: 10.1128/JVI.05047-11.) [PMID: 22156526, PMCID: PMC3302421] Epub 2011 Dec 7.
• Axthelm MK, Bourdette DN, Marracci GH, Su W, Mullaney ET, Manoharan M, Kohama SG, Pollaro J, Witkowski E, Wang P, Rooney WD, Sherman LS, Wong SW. Japanese macaque encephalomyelitis: a spontaneous multiple sclerosis-like disease in a nonhuman Primate. Ann Neurol. 2011 Sep;70(3):362-73. (doi: 10.1002/ana.22449.) [PMID: 21674589, PMCID: PMC3170450] Epub 2011 Jun 14.
• Estep RD, Messaoudi I, O'Connor MA, Li H, Sprague J, Barron A, Engelmann F, Yen B, Powers MF, Jones JM, Robinson BA, Orzechowska BU, Manoharan M, Legasse A, Planer S, Wilk J, Axthelm MK, Wong SW. Deletion of the monkeypox virus inhibitor of complement enzymes locus impacts the adaptive immune response to monkeypox virus in a nonhuman primate model of infection. J Virol. 2011 Sep;85(18):9527-42. (doi: 10.1128/JVI.00199-11.) Epub 2011 Jul 13.
• Messaoudi I, Estep R, Robinson B, Wong SW. Nonhuman primate models of human immunology. Antioxid Redox Signal. 2011 Jan 15;14(2):261-73. (doi: 10.1089/ars.2010.3241.) [PMID: 20524846, PMCID: PMC3014769] Epub 2010 Aug 30.
  Estep RD, Messaoudi I, Wong SW. Simian herpesviruses and their risk to humans. Vaccine. 2010 May 26;28 Suppl 2:B78-84. (doi: 10.1016/j.vaccine.2009.11.026.) [PMID: 20510749, PMCID: PMC2879342]
• Orzechowska BU, Powers MF, Sprague J, Li H, Yen B, Searles RP, Axthelm MK, Wong SW. Rhesus macaque rhadinovirus-associated non-Hodgkin lymphoma: animal model for KSHV-associated malignancies. Blood. 2008 Nov 15;112(10):4227-34. (doi:10.1182/blood-2008-04-151498.) [PMID: 18757778, PMCID: PMC2582004] Epub 2008 Aug 29.
• Jones JM, Messauodi I, Estep RD, Orzechowska B, Wong SW. Monkeypox virus viral chemokine inhibitor (MPV vCCI), a potent inhibitor of rhesus macrophage inflammatory protein-1. Cytokine. 2008 Aug;43(2):220-8. (doi: 10.1016/j.cyto.2008.05.016.) [PMID: 18639466, PMCID: PMC2547134] Epub 2008 Jul 17.
• Estep RD, Powers MF, Yen BK, Li H, Wong SW. Construction of an infectious rhesus rhadinovirus bacterial artificial chromosome for the analysis of Kaposi's sarcoma-associated herpesvirus-related disease development. J Virol. 2007 Mar;81(6):2957-69. [PMID: 17215283, PMCID: PMC1866001] Epub 2007 Jan 10
• Langlais CL, Jones JM, Estep RD, Wong SW. Rhesus rhadinovirus R15 encodes a functional homologue of human CD200. J Virol. 2006 Mar;80(6):3098-103. [PMID: 16501121, PMCID: PMC1395433]
• Hammarlund E, Lewis MW, Carter SV, Amanna I, Hansen SG, Strelow LI, Wong SW, Yoshihara P, Hanifin JM, Slifka MK. Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox. Nat Med. 2005 Sep;11(9):1005-11. [PMID: 16086024] Epub 2005 Aug 7.
• Pratt CL, Estep RD, Wong SW. Splicing of rhesus rhadinovirus R15 and ORF74 bicistronic transcripts during lytic infection and analysis of effects on production of vCD200 and vGPCR. J Virol. 2005 Mar;79(6):3878-82. [PMID: 15731284, PMCID: PMC1075676]
• Hansen SG, Strelow LI, Franchi DC, Anders DG, Wong SW. Complete sequence and genomic analysis of rhesus cytomegalovirus. J Virol. 2003 Jun;77(12):6620-36. [PMID: 12767982, PMCID: PMC156187]
• Estep RD, Axthelm MK, Wong SW. A G protein-coupled receptor encoded by rhesus rhadinovirus is similar to ORF74 of Kaposi's sarcoma-associated herpesvirus. J Virol. 2003 Feb;77(3):1738-46. [PMID: 12525607, PMCID: PMC140923]