Abstract

HIV-1-specific CTL in the genital and gut-associated mucosa is hypothesized to play an important role in controlling dissemination of HIV infection from mucosal tissues to the periphery and may be able to be induced by vaccination. To investigate these possibilities, three specific aims are proposed: To identify viral and host factors associated with the induction and maintenance of mucosal CTL in primary and clinically stable HIV-1 infection; to determine whether mucosal CTL can prevent dissemination of HIV-1 in repeatedly exposed but uninfected persons, and to determine if HIV-1 specific CTL can be induced in the genital tract and mucosa through vaccines administered mucosally. Evaluation of CTL activity will include determination of precursor (p)CTL frequency, epitope specificities, and recognition of autologous HIV-1 strains. Correlations between HIV-1 levels and CTL activity in the peripheral blood and mucosa will be performed in patients with primary infections and on anti-viral therapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI035605-08
Application #
6322314
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Program Officer
Sharma, Opendra K
Project Start
1996-11-01
Project End
2002-10-31
Budget Start
2000-11-01
Budget End
2001-10-31
Support Year
8
Fiscal Year
2001
Total Cost
$359,190
Indirect Cost

  Institution

Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Ballweber, Lamar; Robinson, Barry; Kreger, Allison et al. (2011) Vaginal langerhans cells nonproductively transporting HIV-1 mediate infection of T cells. J Virol 85:13443-7
McElrath, M Juliana; Ballweber, Lamar; Terker, Andrew et al. (2010) Ex vivo comparison of microbicide efficacies for preventing HIV-1 genomic integration in intraepithelial vaginal cells. Antimicrob Agents Chemother 54:763-72
Crawford, D C; Zheng, N; Speelmon, E C et al. (2009) An excess of rare genetic variation in ABCE1 among Yorubans and African-American individuals with HIV-1. Genes Immun 10:715-21
Liu, Yi; Woodward, Amanda; Zhu, Haiying et al. (2009) Preinfection human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes failed to prevent HIV type 1 infection from strains genetically unrelated to viruses in long-term exposed partners. J Virol 83:10821-9
Speelmon, Emily C; Livingston-Rosanoff, Devon; Desbien, Anthony L et al. (2008) Impaired viral entry cannot explain reduced CD4+ T cell susceptibility to HIV type 1 in certain highly exposed individuals. AIDS Res Hum Retroviruses 24:1415-27
Hladik, Florian; McElrath, M Juliana (2008) Setting the stage: host invasion by HIV. Nat Rev Immunol 8:447-57
Hladik, Florian; Sakchalathorn, Polachai; Ballweber, Lamar et al. (2007) Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity 26:257-70
Liu, Huanliang; Carrington, Mary; Wang, Chunhui et al. (2006) Repeat-region polymorphisms in the gene for the dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related molecule: effects on HIV-1 susceptibility. J Infect Dis 193:698-702
Moodie, Zoe; Huang, Yunda; Gu, Lin et al. (2006) Statistical positivity criteria for the analysis of ELISpot assay data in HIV-1 vaccine trials. J Immunol Methods 315:121-32
Speelmon, Emily C; Livingston-Rosanoff, Devon; Li, Shuying Sue et al. (2006) Genetic association of the antiviral restriction factor TRIM5alpha with human immunodeficiency virus type 1 infection. J Virol 80:2463-71

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