At the end of 2000 it was estimated that over 36 million people were living with the human immunodeficiency virus. The introduction of HAART regimens (Highly Active Antiretroviral Therapy) has significantly modified the course of HIV disease, with longer survival rates and improvement of life quality in HIV-infected individuals. However, complete eradication of HIV infection cannot be achieved with currently available antiretroviral regimens. This primarily results from the establishment of a pool of latently infected CD4+ T cells during the very earliest stages of acute HIV infection that persists with an extremely long half-life. This persistence of HIV-1 within resting CD4+ T cells and macrophages constitutes a major obstacle in the control of HIV-1 infection.
The aims are developed to document the capacity and variation in the ability of oral microorganisms to activate HIV(1), to evaluate the ability of oral microorganisms to stimulate resident host cells releasing mediators that would activate HIV-1, and to determine cellular receptors that contribute to this process. The General Hypothesis is that: Oral microorganisms associated with chronic periodontal infections can activate T cells and/or macrophages latently infected with HIV-1, leading to viral recrudescence.
Specific Aim a: To determine the capacity of selected oral microorganisms to activate HIV-1 in latently infected T lymphocytes and macrophages. The hypothesis to be tested is: Selected oral microorganisms comprising the oral biofilm in chronic periodontal infections will activate HIV-1 in latently infected T cells and macrophages. We will use model T cell a macrophage cell lines (1G5; BF24, transfected with the HIV promoter) and (J1.1; OM10.1, reactivation of HIV-1) in these studies.
Specific Aim 2 : To determine the ability of selected oral microorganisms to elicit mediators from resident cell populations that can activate HIV-1 in latently infected T lymphocytes and macrophages. The hypothesis to be tested is: Mediators produced by fibroblasts and epithelial cells stimulated with oral microorganisms will activate HIV in latently infected T cells and macrophages.
Specific Aim 3 : To determine the target receptors for bacterial and host stimulation of the HIV promoter and HIV reactivation in latently infected T cell and macrophages. The hypothesis to be tested is: There are specific receptors on the latently infected T cells and macrophages that will bind bacterial or host ligands, transducing an intracellular signal leading to activation of HIV. Chronic periodontitis, which represents the clinical presentation of the most ubiquitous infection of mankind, has not be examined for a link altering the persistant viral reservoir in HIV infection. The ability to document that the chronic infection triggering periodontitis, which can also be manifest by peripheral translocation of bacteria, has the capacity to activate latently infected T lymphocytes and/or macrophages could have a substantial impact on understanding oral-systemic disease linkages in HIV infection. The potential that the oral bacterial pathogens could contribute to this inter-cellular signaling would also add to a clearer insight into HAART therapy success/failure, as well as long-term strategies to impact HIV reservoirs. Prevention and intervention for periodontitis are very cost-effective measures, thus, including this strategy into the basic health improvement/maintenance of HIV-infected individuals could have significant public health benefits.
Showing the most recent 10 out of 83 publications
