Mycobacteria tuberculosis (MTB) is a worldwide infection whose prevalence has increased in part due to HIV infection. Epidemiological data have demonstrated that HIV-infected individuals are more susceptible to MTB infection and disease. The purpose of this study was to delineate how MTB modulates HIV infection in vivo and in in vivo models. We measured plasma viral load, a direct reflection of lymphoid viral replication, in HIV-infected individuals before, during, and after active MTB disease. It has been observed that the plasma viral load of HIV-infected individuals is increased during the acute phase of MTB disease compared to before the onset of the disease and after treatment. To evaluate the mechansims involved in MTB-induced HIV replication, we studied the virologic and immunologic responses induced by MTB and the constituent antigen PPD in an in vitro system using primary PBMC and lymph node cells isolated from HIV-infected individuals. The data demonstrated that MTB induced HIV replication in vitro in CD8 depleted lymphocytes of HIV- infected individuals with a history of PPD positivity in the absence of exogenous stimulation. The increase of MTB- or PPD-mediated increase in HIV production correlated with the level of cellular activation as demonstrated by an expansion of CD4+, CD25+ cells and by an increase in cellular proliferation. We have also demonstrated that MTB and PPD increased viral replication in an acute infection model where PBMC from healthy donors with positive skin tests for PPD have been infected with HIV-1 primary isolates, and this effect was correlated with the level of cellular activation and proliferation. In conclusion MTB increased viral replication in vivo and in an in vitro model. This MTB-mediated viral production likely occurs through the activation and infection of responding T cells. We believe that these findings may be important to further delineate the immunopathogenic mechanisms of HIV disease and to develop therapeutic strategies based on a knowledge of these mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000720-01
Application #
5200604
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code