Abstract

Based on evidence gathered by these and other investigators, the applicants hypothesize that a single virus strain, rather than multiple variants, are transmitted during initial infection. They suggest that this single strain then replicates to high titer and can lead to the high level viremia detected in some acute infections. Virus-specific immunity is induced, which then controls the viremia. This proposal seeks to address these hypotheses by characterizing the following virologic and immunologic parameters during acute seroconversion: (1) the genotype and phenotype of transmitted viruses, (2) the HIV-1-specific cytotoxic T lymphocyte response, and (3) the HIV-1-specific antibody response. These studies of the interaction between HIV-1 and the immune system during primary infection should provide for a definition of the immediate events surrounding transmission and seroconversion, and they may have important implications for vaccine design and our understanding of viral pathogenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI035522-01A1
Application #
2071245
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1994-05-01
Project End
1998-01-31
Budget Start
1994-05-01
Budget End
1995-01-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Aaron Diamond AIDS Research Center
Department
Type
DUNS #
786658872
City
New York
State
NY
Country
United States
Zip Code
10016

  Publications

Kuhrt, David; Faith, Seth; Hattemer, Angela et al. (2011) Naïve and memory B cells in the rhesus macaque can be differentiated by surface expression of CD27 and have differential responses to CD40 ligation. J Immunol Methods 363:166-76
Kuhrt, David; Faith, Seth A; Leone, Amanda et al. (2010) Evidence of early B-cell dysregulation in simian immunodeficiency virus infection: rapid depletion of naïve and memory B-cell subsets with delayed reconstitution of the naïve B-cell population. J Virol 84:2466-76
Leone, Amanda; Rohankhedkar, Mukta; Okoye, Afam et al. (2010) Increased CD4+ T cell levels during IL-7 administration of antiretroviral therapy-treated simian immunodeficiency virus-positive macaques are not dependent on strong proliferative responses. J Immunol 185:1650-9
Pandrea, Ivona; Sodora, Donald L; Silvestri, Guido et al. (2008) Into the wild: simian immunodeficiency virus (SIV) infection in natural hosts. Trends Immunol 29:419-28
Kosub, David A; Lehrman, Ginger; Milush, Jeffrey M et al. (2008) Gamma/Delta T-cell functional responses differ after pathogenic human immunodeficiency virus and nonpathogenic simian immunodeficiency virus infections. J Virol 82:1155-65
Kosub, David A; Durudas, Andre; Lehrman, Ginger et al. (2008) Gamma/Delta T cell mRNA levels decrease at mucosal sites and increase at lymphoid sites following an oral SIV infection of macaques. Curr HIV Res 6:520-30
Gordon, Shari N; Klatt, Nichole R; Bosinger, Steven E et al. (2007) Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys. J Immunol 179:3026-34
Estes, Jacob D; Wietgrefe, Stephen; Schacker, Timothy et al. (2007) Simian immunodeficiency virus-induced lymphatic tissue fibrosis is mediated by transforming growth factor beta 1-positive regulatory T cells and begins in early infection. J Infect Dis 195:551-61
Milush, Jeffrey M; Reeves, Jacqueline D; Gordon, Shari N et al. (2007) Virally induced CD4+ T cell depletion is not sufficient to induce AIDS in a natural host. J Immunol 179:3047-56
Milush, Jeffrey M; Stefano-Cole, Kelly; Schmidt, Kimberli et al. (2007) Mucosal innate immune response associated with a timely humoral immune response and slower disease progression after oral transmission of simian immunodeficiency virus to rhesus macaques. J Virol 81:6175-86

Showing the most recent 10 out of 57 publications