Molecular Mechanisms of HIV-1 Latency and Its Breakdown by Periodontal Diseases

Twenty-seven years after the discovery of HIV-1 in 1983, we are still unable to eliminate the virus from infected patients. A highly active antiretroviral therapy (HAART), using combinations of antiretroviral agents, efficiently decreases the HIV-1 load to below the limit of detection, reducing mortality due to HIV-1 infection. Despite the potency of HAART, however, latent HIV-1 infection is established in reservoir of resting CD4+ T cells, escaping host immune responses and antiretroviral therapy. HIV-1 latency is thus the main obstacle to eradicating of the virus from infected patients. A causal link between infection by various microbes in HIV-infected individuals and disease progression of AIDS has been documented in the context of the ability of coinfecting microbes and their products to augment HIV-1 replication. Although HIV-related oral lesions are known to be early signs of HIV-1 infection, the causal relationship between periodontal disease and HIV-1 infection has not been elucidated. Recently, we found that the periodontopathic bacterium Porphyromonas gingivalis could induce HIV-1 reactivation via chromatin modification, and that the bacterial metabolites butyric acid is responsible for this effect. Our observations suggest that periodontal diseases could act as a risk factor for HIV-1 reactivation in infected individuals and might contribute to systemic dissemination of the virus. This review attempts to evaluate the current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency, and presents a hypothetic model for the potential role of periodontitis as a risk factor for HIV-1 activation in infected individuals.