Project: Research project

Project Details


A fundamental issue in the pathogenesis of AIDS regards the primary
factors which influence viral burden during disease progression. As the
major reservoirs for HIV-1 replication, CD4+ T lymphocytes and
macrophages play a central role in the maintenance of viral burden,
however, replication of HIV-1 within these cells is profoundly influenced
by their activation state. As an extension of this, opportunistic
pathogens of the lung may influence HIV replication in infected
individuals directly by activation of HIV replication in lung
macrophages. Additionally, cytokines released from activated macrophages
may indirectly activate HIV replication in CD4+T lymphocytes. Either
scenario would exacerbate viral burden in the infected individual.

The approach to be taken in examining activation of HIV-1 by antigens of
Streptococcus pneumoniae, a major lung pathogen, stems from our recent
observations that pneumococcal vaccination of HIV-1 infected individuals
leads to significant yet transient increases in viral burden. This
proposal aims to examine how pneumococcal antigens influence HIV
replication in macrophages and CD4+T lymphocytes and additionally to
identify viral and cellular determinants which mediate this effect.
Specifically we propose to:

1. Examine the effect of pneumococcal antigens on HIV-1 replication in
macrophages in vitro.

2. Examine role of CD4+ T lymphocytes in activation of HIV by antigens
of S. pneumoniae.

3. Examine impact of pneumococcal vaccination and acute pneumococcal
infection on viral burden in HIV-1 infected individuals.

It is expected that these studies will provide insight into how
opportunistic pathogens of the lung impact HIV replication and further
delineate the mechanism of HIV-1 activation.
Effective start/end date9/29/967/31/01


  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute: $268,750.00
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute


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