Nonhuman primates have long been recognized for their value as comparative models for basic human infectious disease pathogenesis research; human vaccine development, efficacy testing and safety evaluation; and for the investigation of fundamental questions in basic immunology.

Michael Axthelm and his team focus on improving nonhuman primates for use as models for AIDS-related research, nonhuman primate virology and developing new nonhuman primate models for human viral diseases. His laboratory is developing major histocompatibility complex-defined, specific pathogen free rhesus macaque breeding resources. The overall goal is to enhance the rhesus macaque as a model for investigating viral pathobiology and immunobiology, and vaccine development relevant to human HIV infection and AIDS-related opportunistic infections.

Current research projects include 1) investigation of the role of T cell dynamics in simian immunodeficiency virus (SIV) infection, and delineation of viral mechanisms of pathogenesis targeting these dynamics, 2) development of rhesus cytomegalovirus-vectored vaccines for SIV, 3) evaluating mucosal vaccine strategies against SIV/HIV, 4) vaccine strategies for emerging viral and bacterial diseases and 5) identification and characterization of new viral agents and viral-associated disease states in nonhuman primates, which currently include spontaneous multiple sclerosis-like demyelinating encephalomyelitis associated with a novel gammma-2 herpesvirus, and progressive multifocal leukoencephalopathy in immunosuppressed macaques associated with variant simian virus 40 polyomavirus.

Off-site and collaborating scientists receive resources and expertise for nonhuman primate infectious disease studies through an Infectious Disease-related Nonhuman Primate Research Protocol Management and Support Program directed by Dr. Axthelm. The program also aids new Center investigators in their transition from small animal- or human –based research programs to nonhuman primates.

Biography

Dr. Axthelm completed his D.V.M. degree and pathology residency program at Kansas State University and is a board-certified veterinary anatomic pathologist. He then went to the Ohio State University for postdoctoral training and received his Ph.D. In viral pathogenesis degree in 1985. He was an assistant professor at the Ohio State University College of Veterinary Medicine until joining the Primate Research Center staff in 1986. Currently, Dr. Axthelm is an associate scientist in the Division of Pathobiology and Immunology, Oregon National Primate Research Center, and Senior Scientist in the Vaccine and Gene Therapy Institute.

Publications

• Fukazawa Y, Lum R, Okoye AA, Park H, Matsuda K, Bae JY, Hagen SI, Shoemaker R, Deleage C, Lucero C, Morcock D, Swanson T, Legasse AW, Axthelm MK, Hesselgesser J, Geleziunas R, Hirsch VM, Edlefsen PT, Piatak M Jr, Estes JD, Lifson JD, Picker LJ. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. Nat Med. 2015 Jan 19. doi: 10.1038/nm.3781. [PMID: 25599132] Epub ahead of print.
• 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, PMCID: PMC4304765] Epub 2014 Nov 19.
• Engelmann F, Josset L, Girke T, Park B, Barron A, Dewane J, Hammarlund E, Lewis A, Axthelm MK, Slifka MK, Messaoudi I. Pathophysiologic and transcriptomic analyses of viscerotropic yellow fever in a rhesus macaque model. PLoS Negl Trop Dis. 2014 Nov 20;8(11):e3295. (doi: 10.1371/journal.pntd.0003295.) [PMID: 25412185, PMCID: PMC4238990] eCollection 2014.
• 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.
• Malouli D, Howell GL, Legasse AW, Kahl C, Axthelm MK, Hansen SG, Früh K. Full genome sequence analysis of a novel adenovirus of rhesus macaque origin indicates a new simian adenovirus type and species. Virol Rep. 2014 Sep;3-4:18-29. [PMID: 25530944, PMCID: PMC4266990]
• Pal P, Fox JM, Hawman DW, Huang YJ, Messaoudi I, Kreklywich C, Denton M, Legasse AW, Smith PP, Johnson S, Axthelm MK, Vanlandingham DL, Streblow DN, Higgs S, Morrison TE, Diamond MS. Chikungunya viruses that escape monoclonal antibody therapy are clinically attenuated, stable, and not purified in mosquitoes. J Virol. 2014 Aug;88(15):8213-26. (doi: 10.1128/JVI.01032-14.) [PMID: 24829346, PMCID: PMC4135940] Epub 2014 May 14.
• 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.
• 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.
• Hansen SG, Piatak M Jr, Ventura AB, Hughes CM, Gilbride RM, Ford JC, Oswald K, Shoemaker R, Li Y, Lewis MS, Gilliam AN, Xu G, Whizin N, Burwitz BJ, Planer SL, Turner JM, Legasse AW, Axthelm MK, Nelson JA, Früh K, Sacha JB, Estes JD, Keele BF, Edlefsen PT, Lifson JD, Picker LJ. Immune clearance of highly pathogenic SIV infection. Nature. 2013 Oct 3;502(7469):100-4. (doi: 10.1038/nature12519.) [PMID: 24025770, PMCID: PMC3849456] Epub 2013 Sep 11.
• Jaworski JP, Kobie J, Brower Z, Malherbe DC, Landucci G, Sutton WF, Guo B, Reed JS, Leon EJ, Engelmann F, Zheng B, Legasse A, Park B, Dickerson M, Lewis AD, Colgin LM, Axthelm M, Messaoudi I, Sacha JB, Burton DR, Forthal DN, Hessell AJ, Haigwood NL. Neutralizing polyclonal IgG present during acute infection prevents rapid disease onset in simian-human immunodeficiency virus SHIVSF162P3-infected infant rhesus macaques. J Virol. 2013 Oct;87(19):10447-59. (doi: 10.1128/JVI.00049-13.) [PMID: 23885083, PMCID: PMC3807376] Epub 2013 Jul 24.
• Hansen SG, Sacha JB, Hughes CM, Ford JC, Burwitz BJ, Scholz I, Gilbride RM, Lewis MS, Gilliam AN, Ventura AB, Malouli D, Xu G, Richards R, Whizin N, Reed JS, Hammond KB, Fischer M, Turner JM, Legasse AW, Axthelm MK, Edlefsen PT, Nelson JA, Lifson JD, Früh K, Picker LJ. Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science. 2013 May 24;340(6135):1237874. (doi: 10.1126/science.1237874.) [PMID: 23704576, PMCID: PMC3816976]
• Park H, Adamson L, Ha T, Mullen K, Hagen SI, Nogueron A, Sylwester AW, Axthelm MK, Legasse A, Piatak M Jr, Lifson JD, McElrath JM, Picker LJ, Seder RA. Polyinosinic-polycytidylic acid is the most effective TLR adjuvant for SIV Gag protein-induced T cell responses in nonhuman primates. J Immunol. 2013 Apr 15;190(8):4103-15. (doi: 10.4049/jimmunol.1202958.) [PMID: 23509365, PMCID: PMC3622154] Epub 2013 Mar 15.
• 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.
• Fukazawa Y, Park H, Cameron MJ, Lefebvre F, Lum R, Coombes N, Mahyari E, Hagen SI, Bae JY, Reyes MD 3rd, Swanson T, Legasse AW, Sylwester A, Hansen SG, Smith AT, Stafova P, Shoemaker R, Li Y, Oswald K, Axthelm MK, McDermott A, Ferrari G, Montefiori DC, Edlefsen PT, Piatak M Jr, Lifson JD, Sékaly RP, Picker LJ. Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines. Nat Med. 2012 Nov;18(11):1673-81. (doi: 10.1038/nm.2934.) [PMID: 22961108, PMCID: PMC3493820] Epub 2012 Sep 9.
• Okoye AA, Rohankhedkar M, Abana C, Pattenn A, Reyes M, Pexton C, Lum R, Sylwester A, Planer SL, Legasse A, Park BS, Piatak M Jr, Lifson JD, Axthelm MK, Picker LJ. Naive T cells are dispensable for memory CD4+ T cell homeostasis in progressive simian immunodeficiency virus infection. J Exp Med. 2012 Apr 9;209(4):641-51. (doi: 10.1084/jem.20112071.) [PMID: 22451717, PMCID: PMC3328373] Epub 2012 Mar 26.
• 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.
• 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.) [PMID: 21752919, PMCID: PMC3165757] Epub 2011 Jul 13.
• Cicin-Sain L, Sylwester AW, Hagen SI, Siess DC, Currier N, Legasse AW, Fischer MB, Koudelka CW, Axthelm MK, Nikolich-Zugich J, Picker LJ. Cytomegalovirus-specific T cell immunity is maintained in immunosenescent rhesus macaques. J Immunol. 2011 Aug 15;187(4):1722-32. (doi: 10.4049/jimmunol.1100560.) [PMID: 21765018, PMCID: PMC3151292] Epub 2011 Jul 15.
• Hansen SG, Ford JC, Lewis MS, Ventura AB, Hughes CM, Coyne-Johnson L, Whizin N, Oswald K, Shoemaker R, Swanson T, Legasse AW, Chiuchiolo MJ, Parks CL, Axthelm MK, Nelson JA, Jarvis MA, Piatak M Jr, Lifson JD, Picker LJ. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature. 2011 May 26;473(7348):523-7. (doi: 10.1038/nature10003.) [PMID: 21562493, PMCID: PMC3102768] Epub 2011 May 11.
• Cicin-Sain L, Smyk-Pearson S, Currier N, Byrd L, Koudelka C, Robinson T, Swarbrick G, Tackitt S, Legasse A, Fischer M, Nikolich-Zugich D, Park B, Hobbs T, Doane CJ, Mori M, Axthelm MK, Lewinsohn DA, Nikolich-Zugich J. Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates. J Immunol. 2010 Jun 15;184(12):6739-45. (doi: 10.4049/jimmunol.0904193.) [PMID: 20483749, PMCID: PMC3504654] Epub 2010 May 17.
• Hansen SG, Powers CJ, Richards R, Ventura AB, Ford JC, Siess D, Axthelm MK, Nelson JA, Jarvis MA, Picker LJ, Früh K. Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus. Science. 2010 Apr 2;328(5974):102-6. (doi: 10.1126/science.1185350.) [PMID: 20360110, PMCID: PMC2883175]
• Okoye A, Park H, Rohankhedkar M, Coyne-Johnson L, Lum R, Walker JM, Planer SL, Legasse AW, Sylwester AW, Piatak M Jr, Lifson JD, Sodora DL, Villinger F, Axthelm MK, Schmitz JE, Picker LJ. Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis. J Exp Med. 2009 Jul 6;206(7):1575-88. (doi: 10.1084/jem.20090356.) [PMID: 19546246, PMCID: PMC2715089] Epub 2009 Jun 22.
• Hansen SG, Vieville C, Whizin N, Coyne-Johnson L, Siess DC, Drummond DD, Legasse AW, Axthelm MK, Oswald K, Trubey CM, Piatak M Jr, Lifson JD, Nelson JA, Jarvis MA, Picker LJ. Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nat Med. 2009 Mar;15(3):293-9. (doi: 10.1038/nm.1935.) [PMID: 19219024, PMCID: PMC2720091] Epub 2009 Feb 15.
• Novy MJ, Duffy L, Axthelm MK, Sadowsky DW, Witkin SS, Gravett MG, Cassell GH, Waites KB. Ureaplasma parvum or Mycoplasma hominis as sole pathogens cause chorioamnionitis, preterm delivery, and fetal pneumonia in rhesus macaques. Reprod Sci. 2009 Jan;16(1):56-70. (doi: 10.1177/1933719108325508.) [PMID: 19122105] Epub 2009 Jan 2.
• 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.
• Cicin-Sain L, Messaoudi I, Park B, Currier N, Planer S, Fischer M, Tackitt S, Nikolich-Zugich D, Legasse A, Axthelm MK, Picker LJ, Mori M, Nikolich-Zugich J. Dramatic increase in naive T cell turnover is linked to loss of naive T cells from old primates. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19960-5. [PMID: 18056811, PMCID: PMC2148405] Epub 2007 Dec 4.
• Okoye A, Meier-Schellersheim M, Brenchley JM, Hagen SI, Walker JM, Rohankhedkar M, Lum R, Edgar JB, Planer SL, Legasse A, Sylwester AW, Piatak M Jr, Lifson JD, Maino VC, Sodora DL, Douek DC, Axthelm MK, Grossman Z, Picker LJ. Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection. J Exp Med. 2007 Sep 3;204(9):2171-85. [PMID: 17724130, PMCID: PMC2118701] Epub 2007 Aug 27.
• Picker LJ, Hagen SI, Lum R, Reed-Inderbitzin EF, Daly LM, Sylwester AW, Walker JM, Siess DC, Piatak M Jr, Wang C, Allison DB, Maino VC, Lifson JD, Kodama T, Axthelm MK. Insufficient production and tissue delivery of CD4+ memory T cells in rapidly progressive simian immunodeficiency virus infection. J Exp Med. 2004 Nov 15;200(10):1299-314. [PMID: 15545355, PMCID: PMC2211921]
• Axthelm MK, Koralnik IJ, Dang X, Wüthrich C, Rohne D, Stillman IE, Letvin NL. Meningoencephalitis and demyelination are pathologic manifestations of primary polyomavirus infection in immunosuppressed rhesus monkeys. J Neuropathol Exp Neurol. 2004 Jul;63(7):750-8. [PMID: 15290900]
• 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]
• Pitcher CJ, Hagen SI, Walker JM, Lum R, Mitchell BL, Maino VC, Axthelm MK, Picker LJ. Development and homeostasis of T cell memory in rhesus macaque. J Immunol. 2002 Jan 1;168(1):29-43. [PMID: 11751943]