Abstract

This OIG renewal proposal is to continue our studies on the human immunodeficiency viruses types 1 and 2 (HIV-1, HIV-2), the human T cell leukemia viruses types 1 and 2 (HTLV-1, HTLV-2), the human hepatitis B virus )HBV), and the human hepatitis delta virus (HDV). In all cases, emphasis will be on the mechanisms by which the viruses induce disease and the mechanisms of transmission of the viruses. In the cases of HIV-1 we will continue our analysis of the envelope gp120 to determine which epitopes and domains are most important in a functional sense for natural resistance, for vaccine development, and for diagnosis of stage of disease progression or prognosis. Glycosylation sites and disulfide bonds will also be analyzed and new viral proteins will be mapped. Mechanisms by which HIV's cause immunosuppression at the cellular and host level will also be determined. Epidemiological and biological studies will be conducted with HIV-2 to determine the relative virulence and pathogenicity of this virus as compared to HIV-1. The comparative studies will include cell tropism and virus replication load, efficiency of transmission between individuals and between cells in the same person, natural immunogenicity, and role and efficiency of several HIV-2 regulatory genes as compared to HIV-1 regulatory genes. The pathogenesis and epidemiology of HTLV-1 and HTLV-2 will also be analyzed in relation to development of adult T cell leukemia (ATL) and other clinical outcomes. The role of env, tax, rex, and other viral proteins and their domains and representative antibodies will be evaluated for diagnostic prognostic, and transmissibility determinations. The tropism of HTLV's will be analyzed and we will attempt to identify the pol gene products. HBV will be studied in transfected cultured hapatoblastoma cells to elucidate parameters of virus replication and cell deregulation. HBV/HDV interactions will be compared in Africa and the U.S. in relation to liver cancer and other diseases and the West African HDV, which seems different in replication and disease potential, will be characterized.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
2R35CA039805-08
Application #
3479053
Study Section
Special Emphasis Panel (SRC (88))
Project Start
1985-07-01
Project End
1999-04-30
Budget Start
1992-07-01
Budget End
1993-04-30
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Public Health
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Koulinska, Irene N; Villamor, Eduardo; Msamanga, Gernard et al. (2006) Risk of HIV-1 transmission by breastfeeding among mothers infected with recombinant and non-recombinant HIV-1 genotypes. Virus Res 120:191-8
Koulinska, Irene N; Villamor, Eduardo; Chaplin, Beth et al. (2006) Transmission of cell-free and cell-associated HIV-1 through breast-feeding. J Acquir Immune Defic Syndr 41:93-9
Vasan, Ashwin; Renjifo, Boris; Hertzmark, Ellen et al. (2006) Different rates of disease progression of HIV type 1 infection in Tanzania based on infecting subtype. Clin Infect Dis 42:843-52
Renjifo, Boris; Gilbert, Peter; Chaplin, Beth et al. (2004) Preferential in-utero transmission of HIV-1 subtype C as compared to HIV-1 subtype A or D. AIDS 18:1629-36
Kiwelu, Ireen E; Renjifo, Boris; Chaplin, Beth et al. (2003) HIV type 1 subtypes among bar and hotel workers in Moshi, Tanzania. AIDS Res Hum Retroviruses 19:57-64
Koulinska, Irene N; Chaplin, Beth; Mwakagile, Davis et al. (2003) Hypermutation of HIV type 1 genomes isolated from infants soon after vertical infection. AIDS Res Hum Retroviruses 19:1115-23
Renjifo, Boris; Chung, Michael; Gilbert, Peter et al. (2003) In-utero transmission of quasispecies among human immunodeficiency virus type 1 genotypes. Virology 307:278-82
Koulinska, Irene N; Msamanga, Gernard; Mwakagile, Davis et al. (2002) Common genetic arrangements among human immunodeficiency virus type 1 subtype A and D recombinant genomes vertically transmitted in Tanzania. AIDS Res Hum Retroviruses 18:947-56
Ndung'u, T; Renjifo, B; Essex, M (2001) Construction and analysis of an infectious human Immunodeficiency virus type 1 subtype C molecular clone. J Virol 75:4964-72
Gilbert, P B; Novitsky, V A; Montano, M A et al. (2001) An efficient test for comparing sequence diversity between two populations. J Comput Biol 8:123-39

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