Butyric acid, a bacterial metabolite, reactivate latently infected HIV-1

Objectives:Butyric acid, an extracellular metabolite from periodonto pathic bacteria, is detected in human periodontal pockets. And it is thought to play an important role in periodontal diseases. Latently infected cells harbor the HIV-1 proviral DNA integrated in heterochromatins allowing the persistence of transcriptionally-silent proviruses. Hypoacetylation of histone proteins by histone deacetylases (HDACs) is involved in the maintenance of HIV-1 latency by repressing transcription from HIV-1 proviral DNA. Progression of AIDS is associated with development of severe periodontitis. Although it is known that butyric acid, is involved in reactivation of the repressed chromatin, it is not known whether periodontitis is involved in progression of HIV-infection. Thus, we examined whether infection of periodontopathic bacteria could facilitate progression of AIDS by reactivating the latent HIV provirus.

Methods:The culture supernatants and cells from 15 strains of bacteria were employed in this study. ACH-2 and U1 cells, latently infected with HIV-1, were incubated with the tested strains. HIV-1 proteins were detected by immunoblot and ELISA. Luciferase and chromatin immunoprecipitation assays were employed to analyze the HIV transcription. Butyric acid and other short chain fatty acids were measured by gas chromatography.

Results:We found that the culture supernatants of P. gingivalis, F. nucleatum strongly induced HIV-1 replication via chromatin modification and these effects could be ascribed to butyric acid. In summary, we found that P. gingivalis, F. nucleatum produce high concentrations of butyric acid that act as a potent inhibitor of HDACs and appear to induce acetylation of histone, thus eventually leading to reactivation of HIV-1 in latently infected cells.

Conclusions: These results suggested that periodontal diseases could act as a risk-factor for HIV reactivation in the latently infected individuals. This study was supported by Grant from Dental Research Center, Nihon University School of Dentistry.