HIV Compartmentalization in Women:Virus &CTL Response

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant): Investigation of HIV-1 in the genital
tract of women is necessary to develop effective vaccines, therapies, and
strategies to block heterosexual and mother-to-child transmission. The rapid
replication and evolution of HIV-1 coupled with selective pressures exerted by
the host?s immune system leads to a genetically heterogeneous HIV-4 population
known as a quasispecies. Quasispecies exist even in a single individual, with
the degree of genomic variation between viruses from different individuals
usually exceeding that seen within the same person. Such variation presents a
major challenge to vaccine design. Preliminary studies of HIV-1 variation in
the female genital tract vs. plasma provide evidence for viral
compartmentalization, chronic dual infection with different strains in
different compartments, and differential drug resistance. Investigation of the
correlates of compartmentalization will help us to understand the mechanisms of
containment and control of HIV-1 infection. To understand these separate HIV-1
reservoirs as well as mucosal transmission and immunologic control, it is
crucial to investigate the interaction of HIV-1 and the immune response in both
female genital tract and blood. We therefore propose to investigate the role of
cytotoxic T cells (CTL) response in containing HIV-1 strains within the genital
tract or blood. We plan to use state-of-the-art technology to focus on
well-characterized women in the Women's Interagency HIV Study. We shall
emphasize complementary, in-depth, virologic and immunologic studies of the
same individuals. First, by analyzing contemporaneous HIV-I RNA sequences from
genital tract and plasma, we shall identify women displaying HlV-1
compartmentalization, dual infection, and differential drug resistance. Then,
we will investigate CTL responses in a subset of these women by examining the
ability of each woman's systemic and genital tract CTL to recognize epitope
variants representing the viral quasispecies present in her own two body
compartments. We also propose to test whether differential recognition by CTL
at these two sites is mirrored by differences in the epitope specificity of
blood CTL with or without mucosa homing receptors. These studies promise to
increase our understanding of the interactions between host CTL and virus,
which are critical in controlling HIV-1 infection.
StatusFinished
Effective start/end date9/1/026/30/09

Funding

  • National Institutes of Health: $409,969.00
  • National Institutes of Health: $397,896.00
  • National Institutes of Health: $348,009.00
  • National Institutes of Health: $387,415.00
  • National Institutes of Health: $408,699.00

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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