In Tanzania, newborns are infected by HIV-1 subtypes A, C, D and intersubtype recombinants. These HIV-1 subtypes are responsible for almost all HIV-1 infections in infant and adult populations. At the present time, the viral genetic determinant(s) that contribute to perinatal infection are unknown. Our Tanzania mother-child cohort provides a unique population to study the generation of intersubtype recombinants as molecular tools to map viral determinants associated with perinatal transmission in the context of different HIV-1 subtypes. This analysis will include a large number of recombinant genomes with a variety of recombination patterns from transmitting and non- transmitting mothers as well as a detailed genetic analysis of recombinant viruses that were successfully transmitted to infants. To establish if recombinant viruses are better fitted for perinatal transmission than parental genomes, we will sequence a large number of env and gag clones from maternal blood. By comparing the proportion of recombinant viruses in transmitting and non-transmitting mothers we will establish if recombinant viruses have a selective advantage for perinatal transmission. We will sequence full-length recombinant genomes of infected infants to determine if recombinant viruses transmitted perinatally follow particular patterns of genetic exchange associated with increased rates of perinatal transmission. We will sequence full- length recombinant genomes of infected infants to determine if recombinant viruses transmitted perinatally follow particular patterns of genetic exchange associated with increased rates of perinatal transmission. Our preliminary studies suggest that particular regions of the viral genome, such as certain gp120 V3's are over represented in transmitted recombinants. In vitro studies of envelope and LTR regions from recombinant and non-recombinant viruses will give use relevant information about the phenotypes that are generated by the genetic exchange. We believe these studies will contribute to the identification of viral determinants associated with perinatal transmission and to help establish whether genetic differences between HIV-1 subtypes are associated with biological functions. This study may provide information that will eventually be useful for decreasing rates of perinatal infection.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD037783-02
Application #
6151181
Study Section
Special Emphasis Panel (ZRG1-AARR-6 (01))
Program Officer
Nugent, Robert
Project Start
1999-02-01
Project End
2003-01-01
Budget Start
2000-02-01
Budget End
2001-01-31
Support Year
2
Fiscal Year
2000
Total Cost
$207,228
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Public Health
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
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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
Kiwelu, Ireen E; Koulinska, Irene N; Nkya, Watoky M M M et al. (2005) Identification of CRF10_CD viruses among bar and hotel workers in Moshi, Northern Tanzania. AIDS Res Hum Retroviruses 21:897-900
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
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
Koulinska, I N; Ndung'u, T; Mwakagile, D et al. (2001) A new human immunodeficiency virus type 1 circulating recombinant form from Tanzania. AIDS Res Hum Retroviruses 17:423-31

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