Research in the MMD lab comprises a multidisciplinary program aimed at understanding mechanisms by which SIV and SHIV cause persistent infection, AIDS, and disease in the brain. We are also involved in a program comparing the efficacies of live vs. DNA vaccines aimed at prophylactic and therapeutic immunization of animals against disease. Investigators in the lab focus their studies on molecular biology and patho-biology, and extend observations from cell culture systems to translational research in animals. Examples of these are host response genes and vaccines whose expression modulate virus replication.
Joag, SV., Li, Z., Foresman, L., Stephens, EB., Zhao, L-J., Adany, I., Pinson, DM., McClure, HM., Narayan, O. Chimeric simian/human immunodeficiency virus that causes progressive loss of CD4+ T Cells and AIDS in pig-tailed macaques. J. Virology 70: 3189-3197, 1996.
Joag, SV, Adany, I., Li, Z., Foresman, L., Pinson, DM., Wang, C., Stephens, EB., Raghavan, R., Narayan, O. Animal model of mucosally transmitted HIV-1 disease: Intravaginal and oral deposition of SHIV in macaques results in systemic infection, elimination of CD4+ T cells and AIDS. J. Virol. 71:4016-4023, 1997.
Joag, SV., Li, Z., Foresman, L., Pinson, DM., Raghavan, R., Zhuge, W., Adany, I., Wang, C., Jia, F., Sheffer, Ranchalis, J., Watson, A., Narayan, O. Characterization of the pathogenic KU-SHIV model of acquired immunodeficiency syndrome in macaques. AIDS Res. and Human Retroviruses, 13: 635-645, 1997.
Raghavan, R., Joag, S., Adany, I., Pinson, Stephens, E., Li, Z., Foresman, L., Jia, F., Narayan, O. Neuropathogenesis of chimeric simian/human immunodeficiency virus infection in rhesus an pig-tailed macaques. Brain Pathology 7: 851-861. 1997.
Foresman, L., Jia, F., Li, Z., Wang, C., Stephens, E.B., Sahni, M., Narayan, O., Joag, S.V. Neutralizing antibodies prevent infection in macaques inoculated with virulent SHIV. AIDS Res. & Human Retroviruses, 14:1035-1043, 1998.
Zhuge, W., Jia, F., Stephens, EB, Li, Z., Wang, C., Joag, SV, Narayan, O. Failure of SIVmac to be neutralized in macrophage culture is unique to SIVmac and not observed with neutralization of SHIV or HIV-1. AIDS Res. & Human Retroviruses, 14:1045-1051, 1998.
McCormick-Davis, C., Zhao, L., Mukherjee, S., Leung, K., Sheffer, D., Joag, SV., Narayan, O., Stephens, EB. Chronology of genetic changes in the vpu, env and nef genes of chimeric simian-human immunodeficiency virus (strain HXB2) during acquisition of virulence for pig-tailed macaques. Virology:248: 275-283. 1998.
Joag, S.V., Liu, Z.Q., Stephens, E.B., Smith, M.S., Kumar, A., Li, Z., Wang, C., Sheffer, D., Jia, F., Foresman, L., Adany, I., Lifson, J., McClure, H.M., Narayan, O. Oral immunization of macaques with attenuated vaccine virus induced protection against vaginally-transmitted AIDS. J. Virol. 72: 9069-9078, 1998.
Raghavan, R., Cheney, P., Raymond, L.A., Joag, S.V., Stephens, E.B., Adany, I., Pinson, D.M., Li, Z., Marcario, J.K., Jia, F., Foresman, L., Berman, N.E.J., Narayan, O. Morphological correlates of neurological dysfunction in macaques infected with neurovirulent simian immunodeficiency virus. Neuropathol and Applied Biology, 25:285-294,1999.
Narayan, S., Mukherjee, S., Jia, F., Li, Z., Wang, C., Foresman, L., Stephens, E.B., Joag, S.V., Narayan, O. Characterization of a neutralization-escape variant of SHIVKU-,1, a virus that causes Acquired Immune Deficiency Syndrome in pig-tailed macaques. Virology 256:54-63, 1999.
Liu, Z.Q., Mukherjee, S., Sahni, M., Li, Z., Wang, C., Joag, S.V., Gattone II, V.H., Qian, C., Doms, R.W., Hoffman, T.L., Narayan, O., Stephens, E.B. Derivation and biological characterization of a molecular clone of SHIVKU-2 that causes AIDS, neurological and renal disease in rhesus macaques. Virology:260(2):295-307, 1999.
Berman, NEJ, Marcario, J., Yong, C., Raghavan, R., Raymond, LA, Joag, S., Narayan, O., and Cheney, P. Microglial activation and neurological symptoms in the SIV model of NeuroAIDS: Association of MHC-II and MMP-9 expression with behavioral deficits and evoked potential changes. Neurobiology of Disease 6, 488-498, 1999.
Kumar, A., Stipp, H., Sheffer, D., Narayan, O.. Use of herpesvirus saimiri-immortalized macaque CD4+ T cell clones as stimulators and targets for SHIVKU-1 specific CTLs. J. Immunol. Methods 230:47-58, 1999.
Silverstein, P., Mackay, G., Mukherjee, S., Li, Z, Piatak, M., Jr., Lifson, J., Narayan, O., Kumar, A.: 2000. Pathogenic SHIVKU Inoculated into Immunized Macaques Caused Infection, but Virus Burdens Progressively Declined with Time. J. Virol. 74: 10489-10497, 2000.
Stipp, H., Kumar, A., Narayan, O.: Characterization of immune escape viruses from a macaque immunized with live-virus vaccine and challenged with pathogenic SHIV KU-1. AIDS Res. & Human Retroviruses 16: 1573-1580, 2000.
Smith, M.S., Foresman, L., Lopez, G. Tsay, J., Page, A., Wang, C., Li, Z., Adany, I., Lifson, J.D., Bischofberger, N., Narayan, O.: Lasting Effects of Transient Postinoculation Tenofovir [9-R-(2 phosphonomethoxypropyl)adenine] on SHIVKU2 Infection of Rhesus Macaques. Virology 277, 306-315, 2000.
Kumar, A., Lifson, J., Li, Z., Jia, F., Mukherjee, S., Adany, I., Liu, Z., Piatak, M.,Sheffer, D., McClure, H., Narayan, O.: Sequential immunization of Macaques with Two Differentially Attenuated Vaccines Induced Long-Term Virus-Specific Immune Responses and Conferred Protection against AIDS Caused by Heterologous Simian Human Immunodeficiency Virus (SHIV89.6 P). Virology 279: 241-256, 2001.
Zhang, S., Feng, Y., Narayan, O., Zhao, L.J.: Cytoplasmic retention of HIV-1 regulatory protein Vpr by protein-protein interaction with a novel human cytoplasmic protein VprBP. GENE 263:131-140, 2001.
Kumar,A., Narayan, O.: Immunization for Long-Term Protection against AIDS Using the Macaque Model. Virology 285:1-5, 2001.
David, S.A., Smith, M.S., Lopez, G.J., Adany, I., Mukherjee, S., Buch, S., Goodenow, M.M., and , Narayan, O. Selective Transmission of R5-Tropic HIV Type 1 from Dendritic Cells to Resting CD4+ T Cells. AIDS Res & Human Retroviruses, 17:59-68, 2001.
Zhuge, W., Jia, F., Mackay, G., Kumar, A., Narayan, O.: Antibodies that neutralize SIVmac251 in T lymphocytes cause only transient interruption of the viral life cycle in macrophages by preventing nuclear import of viral DNA. Virology 287: 436-445, 2001.
Buch, S., Pinson, D., King, C., Raghavan, R., Hou, Y., Li, Z., Adany, I., Hicks, A., Villinger, F., Kumar, A., Narayan, O.: Inhibitory and enhancing effects if IFN-g and IL-4 on SHIVKU replication in rhesus macaque macrophages: correlation between Th2 cytokines and productive infection in tissue macrophages during late stage infection.. Cytokine 13: 295-304, 2001.
Kumar, A., Mukherjee, S., Shen, J., Buch, S., Li, Z., Adany, I., Liu, Z. Zhuge, W., Piatak, M., Lifson, J., McClure, H., Narayan, O.: Immunization of macaques with live Simian Human Immunodeficiency virus (SHIV) vaccines conferred protection against AIDS induced by homologous and heterologous SHIVs and Simian Immunodeficiency virus (SIV). Virology 301: 189, 2002.
Hicks, A., Potula, R., Villinger, F., Pinson, D., Adany, I., Li, Z., Long, C., Mueller, N., Kumar, A., Major, E., Narayan, O., Buch, S.: Neuropathogenesis of Lentiviral Infection in Macaques: Roles of CXCR4 and CCR5 viruses and IL-4 in Enhancing Monocyte Chemoattractant Protein-1 Production in Macrophages. American J. Pathology 161: 813-822, 2002.
Mackay, G., Niu, Y., Liu, Z., Mukherjee, S., Li, Z., Adany, I., Buch, S., Zhuge, W., McClure, H., Narayan, O., Smith, M.S.: Presence of Intact vpu and nef Genes in Non-Pathogenic SHIV is Essential for Acquisition of Pathogenicity of this Virus by Serial Passage in Macaques. Virology 295: 133-146, 2002.
Buch,S., Villinger, F., Pinson, D., You, Y., Adany, I., Li, Z., Dalal, R., Raghavan, R., Kumar, A., Narayan, O.: Innate differences between Simian-Human Immunodeficiency Virus (SHIV)KU2 infected rhesus and pig-tailed macaques to development of neurological disease. Virology 295: 54-62, 2002.
Smith, M.S., Niu, Y., Li, Z., Adany, I., Pinson, D., Liu, Z., Berry, T., Sheffer, D., Jia, F., Narayan, O.: Systemic Infection and Limited Replication of SHIV Vaccine Virus in Brains of Macaques Inoculated Intracerebrally with Infectious Viral DNA. Virology 301:130-135, 2002.
Turchan, J., Pocernich. C.B., Gairola, C., Chauhan, A., Schifitto, G., Butterfield, D.A., Buch, S., Narayan, O., Sinai, A., Geiger, J., Berger. J.R., Elford H., Nath, A. Oxidative stress in HIV demented patients and protection ex vivo with novel antioxidants. Neurology 60(2):307-14, 2003.
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