Peter A. Barry, Ph.D.
Dr. Barry is a molecular virologist with expertise in the natural history (i.e., virology and immunology) of herpesviruses in nonhuman primates. His laboratory has optimized a model of rhesus cytomegalovirus (RhCMV) to investigate mechanisms of human cytomegalovirus (HCMV) persistence and pathogenesis. RhCMV is a precise recapitulation of all aspects of HCMV. In addition, his laboratory has optimized techniques for the detection of herpes B virus in rhesus macaques.
RhCMV, like HCMV, can establish either latent or persistent, low-level expression following acute viremia. Using the RhCMV model, Dr. Barry’s laboratory is examining the type(s) of infected cells and patterns of viral expression/replication at different stages of infection, and the kinetics and specificity of host immune responses during infection. Considerable effort is being devoted to analysis of RhCMV infection in immunocompetent hosts to form the foundation for pathogenesis and vaccine studies. Special emphasis is being placed on virally encoded proteins that can modulate host immune responses.
Fetuses infected with RhCMV exhibit outcomes very similar to human infants congenitally infected with HCMV. Recent studies indicate that infection of the fetus at earlier times of gestation is more likely to result in severe disease than infection at later times. This is due to decreasing susceptibility of the fetal CNS to damaging infection and increasing levels of protective antiviral antibodies transferred from the mother to the fetus as gestation proceeds. Current and future work is aimed at the mechanisms of pathogenesis associated with intrauterine RhCMV infection, transplacental transport of maternal antibodies to the fetus, identification of immune correlates of protection, and strategies that limit or prevent fetal disease following intrauterine RhCMV infection.
Because there are no current effective vaccines for HCMV, work in the Barry laboratory is directed at vaccination strategies for the prevention of persistent RhCMV infection in immunocompetent hosts. Different methods of vaccination, including DNA immunization, subunit vaccines, attenuated viral vaccines, and combined strategies are being compared, as well as different immunogens. Additional studies are underway to measure the efficacy of vaccination in terms of attenuation of disease. Ongoing studies are directed at determining whether there exists a threshold of antiviral immunity required to protect the host from infection and disease.
Human cytomegalovirus (HCMV) typically establishes lifelong persistent, but asymptomatic, infections in healthy individuals. However, it causes substantial morbidity and mortality in immunocompromised patients (2). Opportunistic infections with HCMV are common in patients with the acquired immune deficiency syndrome (AIDS) or in immunosuppressed solid organ/bone marrow transplant recipients. HCMV is also a leading cause of birth defects following congenital infection of fetuses. The drugs currently approved for treatment of HCMV are limited by toxicity and/or low bioavailability, and there is no licensed vaccine for HCMV. There is a clear need for new and safer treatment options for HCMV disease. Development and testing of new drugs and therapeutic strategies would be greatly enhanced by availability of an animal model system that appropriately models the virology and pathogenesis of HCMV. Our goal is to establish a non-human primate model that will 1) enable rapid in vivo evaluation of promising anti-HCMV drugs, and 2) allow development of therapeutic strategies for HCMV under clinically relevant conditions. Ultimately, we predict that this model can be used to test therapies for CMV infections during AIDS, transplantation, or fetal development in a primate host that can be experimentally manipulated.
Li J, Srivastava T, Rawal R, Isbell D, Tsark W, Barry PA, Rosa CL, Diamond DJ. Mamu-A*01/Kb Transgenic and MHC Class I Knockout Mice as a Tool for HIV Vaccine Development. Virol 387:16-28, 2009. PMC2667874.
White JA, Todd TA, Yee JL, Kalman AL, Yang X, Wong SW, Barry PA, Lerche NW. Prevalence of viremia and oral shedding of two gamma-2-herpesviruses, rhesus rhadinovirus (RRV) and retroperitoneal fibromatosis herpesvirus (RFHV), in large age-structured breeding groups of rhesus macaques (Macaca mulatta). Comp Med 59:383-90, 2009.
Chang W-LW, Barry PA, Szubin R, Wang D, Baumgarth N. Human Cytomegalovirus Suppresses Type I Interferon Secretion by Plasmacytoid Dendritic Cells through Its Interleukin 10 Homolog. Virol 390:330-7, 2009. PMC2747589.
Nicholson IP, Sutherland JS, Chaudry TN, Blewett EL, Barry PA, Nicholl MJ, Preston CM. Properties of virion transactivator proteins encoded by primate cytomegaloviruses. Virol J 6:65-76, 2009. PMC2693105.
Sparger EE, Gardner MB, Barry PA. Exploiting the natural history of cytomegalovirus to vaccinate against HIV. Exp Rev Vaccines 8:993-7, 2009.
Slobedman B, Barry PA, Spencer JV, Avdic S, Abendroth A. Virus encoded homologs of cellular interleukin-10 and their control of host immune function. J Virol 83: 9618-29, 2009. PMC2747999.
Abel K, Strelow L, Yue Y, Eberhardt MK, Schmidt KA, Barry PA. A heterologous DNA prime/protein boost immunization strategy for rhesus cytomegalovirus. Vaccine 26: 6013-25, 2008. PMC2747630.
Engel GA, Pizzaro M, Cortes J, Shaw E, Fuentes A, Lerche N, Barry P, Cohn D, Jones-Engel L. Seroprevalence of antibodies to enzootic simian viruses among the Gibraltar macaques (M. sylvanus). Emerg Infect Dis 14: 1112-5, 2008. PMC2600335.
Lilja AE, Chang WL, Barry PA, Becerra SP, Shenk TE. Functional genetic analysis of rhesus cytomegalovirus: Rh01 is an epithelial cell tropism factor. J Virol 82: 2170-81, 2008. PMC2258942.
Oxford KL, Eberhardt MK, Yang KW, Strelow L, Kelly S, Zhou SS, Barry PA. Protein coding content of the U(L)b' region of wild-type rhesus cytomegalovirus. Virol 373: 181-8, 2008. PMC2766279.
Yue Y, Wang Z, Abel K, Li J, Strelow L, Mandarino A, Eberhardt MK, Schmidt KA, Diamond DJ, Barry PA. Evaluation of Recombinant Modified Vaccinia Ankara Virus-Based Rhesus Cytomegalovirus Vaccines in Rhesus Macaques. Med Microbiol Immunol 197: 117-23, 2008.
Barry PA, Strelow L. Development of Breeding Populations of Rhesus Macaques That Are Specific Pathogen Free for Rhesus Cytomegalovirus. Comp Med 58:43-6, 2008. PMC2703159.
Yue Y, Barry PA. Rhesus Cytomegalovirus: Nonhuman Primates Model for the Study of Human Cytomegalovirus. Adv Virus Res 2:207-26, 2008.
Chang WL, Baumgarth N, Eberhardt MK, Lee CY, Baron CA, Gregg JP, Barry PA. Exposure of myeloid dendritic cells to exogenous or endogenous IL-10 during maturation determines their longevity. J Immunol 178: 7794-804, 2007.
Yue Y, Kaur A, Eberhardt MK, Kassis N, Zhou SS, Tarantal AF, Barry PA. Immunogenicity and protective efficacy of DNA vaccines expressing rhesus cytomegalovirus glycoprotein B, phosphoprotein 65-2, and viral interleukin-10 in rhesus macaques. J Virol 81: 1095-109, 2007. PMC1797524.
Barry PA, Chang W-LW. Primate Herpesviruses, in Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Arvin A, Campadielli G, Moore P, Mocarski E, Roizman B, Whitley R, Yamanishi K, eds. 1051-75 Cambridge University Press, 2007.
Barry PA, Lockridge KM, Salamat S, Tinling SP, Yue Y, Zhou SS, Gospe SM, Jr., Britt WJ, Tarantal AF. Nonhuman primate models of intrauterine cytomegalovirus infection. ILAR J 47: 49-64, 2006.
Jones-Engel L, Engel GA, Heidrich J, Chalise M, Poudel N, Viscidi R, Barry PA, Allan JS, Grant R, Kyes R. Temple monkeys and health implications of commensalism, Kathmandu, Nepal. Emerg Infect Dis 12: 900-6, 2006.
Bell SA, Balasuriya UB, Gardner IA, Barry PA, Wilson WD, Ferraro GL, MacLachlan NJ. Temporal detection of equine herpesvirus infections of a cohort of mares and their foals. Vet Microbiol 116:249-57, 2006.
Khan IH, Mendoza S, Yee J, Deane M, Venkateswaran K, Zhou SS, Barry PA, Lerche NW, Luciw PA. Simultaneous detection of antibodies to six nonhuman-primate viruses by multiplex microbead immunoassay. Clin Vaccine Immunol 13: 45-52, 2006.
Yue Y, Kaur A, Zhou SS, Barry PA. Characterization and immunological analysis of the rhesus cytomegalovirus homologue (Rh112) of the human cytomegalovirus UL83 lower matrix phosphoprotein (pp65). J Genl Virol 87: 777-87, 2006.
Carlson JR, Chang W-LW, Zhou S-S, Tarantal AF, Barry PA. Rhesus Brain Microvascular Endothelial Cells Are Permissive for Rhesus Cytomegalovirus Infection. J Genl Virol 86: 545-9, 2005.
Barry PA, Marthas M, Lerche N, McChesney MB, Miller CJ. Virology Research, in The Handbook of Experimental Animals: The Laboratory Primate: S. Wolfe-Coote, ed.,561-578, Elsevier, 2005.
Barry PA. Efficient Electroporation of Mammalian Cells in Culture. in Gene Delivery to Mammalian Cells: Methods and Protocols, W. Heiser, ed, 2004.
Chang WL, Baumgarth N, Yu D, Barry PA. Human cytomegalovirus-encoded interleukin-10 homolog inhibits maturation of dendritic cells and alters their functionality. J Virol 78: 8720-31, 2004. PMC479089.
Fitzgerald JT, Sena MJ, Vandewalker KN, Johnson JR, Griffey SM, Tarantal AF, Barry PA, McChesney MB, Ramsamooj R, Perez RV. Occult pretransplantation systemic inflammation and posttransplantation vascular changes in a primate arterial allograft model. Transplantation 78: 367-74, 2004.
North TW, Sequar G, Townsend LB, Drach JC, Barry PA. Rhesus cytomegalovirus is similar to human cytomegalovirus in susceptibility to benzimidizole nucleosides. Antimicrob Agents Chemother 48: 2760-5, 2004.
Rue CA, Jarvis MA, Knoche AJ, Meyers HL, DeFilippis VR, Hansen SG, Wagner M, Fruh K, Anders DG, Wong SW, Barry PA, Nelson JA. A cyclooxygenase-2 homologue encoded by rhesus cytomegalovirus is a determinant for endothelial cell tropism. J Virol 78: 12529-36, 2004. PMC434194.
UC Davis Comparative Pathology Graduate Group
UC Davis Microbiology Graduate Group