Abstract

. The long-term objectives of these studies are to define whether in vitro isolation of nucleoside resistant human immunodeficiency virus type 1 (HIV-1) from patients treated with zidovudine (AZT) or dideoxyinosine (ddI) correlates with disease progression, and to directly detect the mutations in HIV-1 reverse transcriptase (RT) that cause clinically significant AZT resistance.
The specific aims are to identify and characterize AZT- and ddI-resistant clinical isolates of HIV-1 and to evaluate the clinical significance of nucleoside resistant HIV isolates and develop an RNA/PCR assay for nucleoside resistant RT genomes in plasma. Finally, it is planned to evaluate the enzymology of AZT resistant RT in order to explain the discrepancy between AZT resistant virion infectivity and the normal RT susceptibility to AZT-TP (triphosphate) in standard assays in vitro.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI029193-02
Application #
3143984
Study Section
Special Emphasis Panel (ARR (V1))
Project Start
1990-07-01
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Donahue, John P; Levinson, Rebecca T; Sheehan, Jonathan H et al. (2015) Genetic analysis of the localization of APOBEC3F to human immunodeficiency virus type 1 virion cores. J Virol 89:2415-24
Song, Chisu; Sutton, Lorraine; Johnson, Megan E et al. (2012) Signals in APOBEC3F N-terminal and C-terminal deaminase domains each contribute to encapsidation in HIV-1 virions and are both required for HIV-1 restriction. J Biol Chem 287:16965-74
Martin, Kenneth L; Johnson, Megan; D'Aquila, Richard T (2011) APOBEC3G complexes decrease human immunodeficiency virus type 1 production. J Virol 85:9314-26
Winham, Stacey J; Slater, Andrew J; Motsinger-Reif, Alison A (2010) A comparison of internal validation techniques for multifactor dimensionality reduction. BMC Bioinformatics 11:394
Vetter, Michael L; D'Aquila, Richard T (2009) Cytoplasmic APOBEC3G restricts incoming Vif-positive human immunodeficiency virus type 1 and increases two-long terminal repeat circle formation in activated T-helper-subtype cells. J Virol 83:8646-54
Vetter, Michael L; Johnson, Megan E; Antons, Amanda K et al. (2009) Differences in APOBEC3G expression in CD4+ T helper lymphocyte subtypes modulate HIV-1 infectivity. PLoS Pathog 5:e1000292
Charles, Macarthur; Noel, Francine; Leger, Paul et al. (2008) Survival, plasma HIV-1 RNA concentrations and drug resistance in HIV-1-infected Haitian adolescents and young adults on antiretrovirals. Bull World Health Organ 86:970-7
Donahue, John P; Vetter, Michael L; Mukhtar, Nizar A et al. (2008) The HIV-1 Vif PPLP motif is necessary for human APOBEC3G binding and degradation. Virology 377:49-53
Koelsch, Kersten K; Liu, Lin; Haubrich, Richard et al. (2008) Dynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro. J Infect Dis 197:411-9
Haas, David W; Geraghty, Daniel E; Andersen, Janet et al. (2006) Immunogenetics of CD4 lymphocyte count recovery during antiretroviral therapy: An AIDS Clinical Trials Group study. J Infect Dis 194:1098-107

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