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.
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.
1: Fukazawa Y, Park H, Cameron MJ, Lefebvre F, Lum R, Coombes N, Mahyari E, Hagen SI, Bae JY, Iii MD, 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. PMCID: PMC3493820
2: Robinson BA, O'Connor MA, Li H, Engelmann F, Poland B, Grant R, DeFilippis VR, 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 March; 86(5): 2769–2779. PMCID: PMC3302252
3: 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 AW, 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 September; 85(18): 9527–9542. PMCID: PMC3165757
4: 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 August 15; 187(4): 1722–1732. PMCID: PMC3151292
5: 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 September; 70(3): 362–373. PMCID: PMC3170450
6: 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): 523–527. PMCID: PMC3102768
7: Wertheimer AM, Uhrlaub JL, Hirsch A, Medigeshi G, Sprague J, Legasse AW, Wilk J, Wiley CA, Didier P, Tesh RB, Murray KO, Axthelm MK, Wong SW, Nikolich-Žugich J. Immune response to the West Nile Virus in aged non-human primates. PLoS One. 2010; 5(12): e15514. PMCID: PMC2996299
8: Leone A, Rohankhedkhar M, Okoye A, Legasse AW, Axthelm MK, Villinger, Piatak M Jr, Lifson JD, Assouline B, Morre M, PickeR LJ, Sodora DL. Increased CD4+ T cell levels during IL-7 administration of ART treated SIV+ macaques are not dependent on strong proliferative responses. J Immunol. 2010 August 1; 185(3): 1650–1659. PMCID: PMC3050806
9: 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 super-infection by cytomegalovirus. Science. 2010 April 2; 328(5974): 102–106. PMCID: PMC2883175
10: Orzechowska BU, Manoharan M, Sprague J, Estep RD, Axthelm MK, Wong SW. Viral interleukin-6 encoded by rhesus macaque rhadinovirus is associated with lymphoproliferative disorder (LPD). J Med Primatol. 2009 October; 38(Suppl 1): 2–7. PMCID: PMC3022225
11: 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, Villinge Fr, 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 July 6; 206(7): 1575–1588. PMCID: PMC2715089
12: Hansen SG, Vieville C, Whizin N, Coyne-Johnson L, Siess D, 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 SIV challenge. Nat Med. 2009 March; 15(3): 293–299. PMCID: PMC2720091
13: 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 November 15; 112(10): 4227–4234. PMCID: PMC2582004
14: Dang X, Wüthrich C, Axthelm MK, Koralnik IJ. Productive SV40 Infection of Neurons in Immunosuppressed Rhesus Monkeys. J Neuropathol Exp Neurol. 2008 August; 67(8): 784–792. PMCID: PMC2745603
15: Murray SM, Picker LJ, Axthelm MK, Hudkins K, Alpers CE, Linial ML. Replication in a superficial epithelial cell niche explains the lack of pathogenicity of primate foamy virus infections. J Virol. 2008 June; 82(12): 5981–5985. PMCID: PMC2395144
16: ?i?in-Šain L, Messaoudi I, Park B, Currier N, Planer S, Fischer M, Tackitt S, Nikolich-Žugich D, Legasse AW, Axthelm MK, PickeR LJ, Mori M, JNikolich-Žugich J. Dramatic increase in naïve T cell turnover is linked to loss of naïve T cells from old primates. Proc Natl Acad Sci U S A. 2007 December 11; 104(50): 19960–19965. PMCID: PMC2148405
17: Gravett MG, Adams KM, Sandosky DW, Grosvenor AR, Witkin SS, Axthelm MK, Novy MJ.
Immunomodulators plus antibiotics delay preterm delivery after experimental intra-amniotic infection in a nonhuman primate model. Am J Obstet Gynecol. 2007 November; 197(5): 518.e1–518.e8. PMCID: PMC2128777
18: Okoye A, Meier-Schellersheim M, Brenchley JM, Hagen SI, Walker JM, Rohankhedkar M, Lum R, Edgar JB, Planer P, Legasse AW, 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 September 3; 204(9): 2171–2185. PMCID: PMC2118701
19: Picker LJ, Reed-Inderbitzin EF, Hagen SI, Edgar JB, Hansen SG, Legasse SW, Planer S, Piatak M Jr, Lifson JD, Maino VC, Axthelm MK, Villinger F. IL-15 induces CD4+ effector memory T cell production and tissue emigration in nonhuman primates. J Clin Invest. 2006 June 1; 116(6): 1514–1524. PMCID: PMC1459071
20: Murray SM, Picker LJ, Axthelm MK, Linial ML. Expanded tissue targets for foamy virus replication with Simian Immunodeficiency Virus-induced immunosuppression. J Virol. 2006 January; 80(2): 663–670. PMCID: PMC1346877
21: Dang X, Axthelm MK, Letvin NL, Koralnik IJ. Rearrangement of Simian Virus 40 regulatory region is not required for induction of progressive multifocal leukoencephalopathy in immunosuppressed Rhesus monkeys. J Virol. 2005 February; 79(3): 1361–1366. PMCID: PMC544112
22: Picker LJ, Hagen SI, Lum R, Reed-Inderbitzin EF, Daly LM, Sylwester AW, Walker JM, Siess D, 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 November 15; 200(10): 1299–1314. PMCID: PMC2211921
23: Hermsmeyer RK, Mishra RG, Pavcnik D, Uchida B, Axthelm MK, Stanczyk FZ, Burry KA, Illingworth RD, Kaski JC, Frank J. Nordt. Prevention of coronary hyperreactivity in preatherogenic menopausal rhesus monkeys by transdermal progesterone. Arterioscler Thromb Vasc Biol. 2004 May; 24(5): 955–961. PMCID: PMC1473191
24: Permar SR, Klumpp SA, Mansfield KG, Kim W-K, Gorgone DA, Lifton MA, Williams KC, Schmitz JE, Reimann KA, Axthelm MK, Polack FP, Griffin DE, Letvin NL. Role of CD8+ lymphocytes in control and clearance of measles virus infection of rhesus monkeys. J Virol. 2003 April; 77(7): 4396–4400. PMCID: PMC150640
25: 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 February; 77(3): 1738–1746. PMCID: PMC140923
26: Margolin DH, Saunders EFH, Bronfin , de Rosa N, Axthelm MK, Alvarez X, Letvin NL. High frequency of virus-specific B lymphocytes in germinal centers of simian-human immunodeficiency virus-infected rhesus monkeys. J Virol. 2002 April; 76(8): 3965–3973. PMCID: PMC136115
27: Etemad-Moghadam B, Rhone D, Steenbeke T, Sun Y, Manola J, Gelman R, Fanton JW, Racz P, Tenner-Racz K, Axthelm MK, Letvin NL, Sodroski J. Membrane-fusing capacity of the human immunodeficiency virus envelope proteins determines the efficiency of CD4+ t-cell depletion in macaques infected by a simian-human immunodeficiency virus. J Virol. 2001 June; 75(12): 5646–5655. PMCID: PMC114277
28: Letvin NL, Robinson S, Rohne D, Axthelm MK, Fanton JW, Bilska M, Palker TJ, Liao X-H, Haynes BF, Montefiori DC. Vaccine-elicited V3 loop-specific antibodies in rhesus monkeys and control of a simian-human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate envelope. J Virol. 2001 May; 75(9): 4165–4175. PMCID: PMC114162
29: Beer BE, Bailes E, Dapolito G, Campbell BJ, Goeken RM, Axthelm MK, Markham PD, Bernard J, Zagury D, Franchini G, Sharp PM, Hirsch VM. Patterns of genomic sequence diversity among their simian immunodeficiency viruses suggest that L'Hoest monkeys (Cercopithecus lhoesti) are a natural lentivirus reservoir. J Virol. 2000 April; 74(8): 3892–3898. PMCID: PMC111899
30: Wong SW, Bergquam EP, Swanson RM, Lee FW, Shiigi SM, Avery NA, Fanton JW, Axthelm MK. Induction of B cell hyperplasia in simian immunodeficiency virus–infected rhesus macaques with the simian homologue of Kaposi's Sarcoma–associated herpesvirus. J Exp Med. 1999 September 20; 190(6): 827–840. PMCID: PMC2195633
31: Bergquam EP, Avery N, Shiigi SM, Axthelm MK, Wong SW. Rhesus rhadinovirus establishes a latent infection in B lymphocytes in vivo. J Virol. 1999 September; 73(9): 7874–7876. PMCID: PMC104320
32: Searles RP, Bergquam EP, Axthelm MK, Wong SW. Sequence and genomic analysis of a rhesus macaque rhadinovirus with similarity to Kaposi’s Sarcoma-associated herpesvirus/human herpesvirus 8. J Virol. 1999 April; 73(4): 3040–3053. PMCID: PMC104064
33: Cayabyab M, Karlsson GB, Etemad-Moghadam BA, Hofmann W, Steenbeke T, Halloran M, Fanton JW, Axthelm MK, Letvin NL, Sodroski JG. Changes in human immunodeficiency virus type 1 envelope glycoproteins responsible for the pathogenicity of a multiply passaged simian-human immunodeficiency virus (SHIV-HXBc2). J Virol. 1999 February; 73(2): 976–984.
34: Karlsson GB, Halloran M, Schenten D, Lee J, Racz P, Tenner-Racz K, Manola J, Gelman R, Etemad-Moghadam B, Desjardins E, Wyatt R, Gerard NP, Marcon L, Margolin D, Fanton JW, Axthelm MK, Letvin NL, Sodroski J. The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian–human immunodeficiency virus–infected macaques. J Exp Med. 1998 September 21; 188(6): 1159–1171. PMCID: PMC2212530
35: Karlsson GB, Halloran M, Li J, Park IW, Gomila R, Reimann KA, Axthelm MK, Iliff SA, Letvin NL, Sodroski J. Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys. J Virol. 1997 June; 71(6): 4218–4225. PMCID: PMC191636
36: Endres CL, Bergquam EP, Axthelm MK, Wong SW. Suppression of simian immunodeficiency virus replication by human immunodeficiency virus type 1 trans-dominant negative Rev mutants. J Virol. 1995 August; 69(8): 5164–5166. PMCID: PMC189339
37: Marracci GH, Kelley RD, Pilchr KY, Crabtree L, Shiigi SM, Avery N, Leo G, Webb MC, Hallick LM, Axthelm MK, et al. Simian AIDS type D serogroup 2 retrovirus: isolation of an infectious molecular clone and sequence analyses of its envelope glycoprotein gene and 3' long terminal repeat. J Virol. 1995 April; 69(4): 2621–2628. PMCID: PMC188942
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