Paper: Reactivation of latent HIV-1 by Porphyromonas gingivalis involves histone modification (IADR/AADR/CADR 87th General Session and Exhibition (April 1-4, 2009))

1703 Reactivation of latent HIV-1 by Porphyromonas gingivalis involves histone modification

Friday, April 3, 2009: 10:45 a.m. - 12:15 p.m.
Location: D233 (Miami Beach Convention Center)
K. OCHIAI1, K. IMAI2, and T. OKAMOTO2, 1Nihon University, Tokyo, Japan, 2Nagoya City University, Nagoya, Japan
Objectives: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 a bacterial metabolite, 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 P. gingivalis infection could facilitate progression of AIDS by reactivating the latent HIV provirus. Methods:ACH-2 and U1 cells, latently infected with HIV-1, were incubated with various components of P. gingivalis. 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 supernatant of P. gingivalis strongly induced HIV-1 replication via chromatin modification and these effects could be ascribed to butyric acid. No such activity was found with neither the fimbriae nor LPS components of P. gingivalis. In summary, we found that P. gingivalis produces high concentrations of butyric acid that acts as a potent inhibitor of HDACs and appears to induce acetylation of histone, thus eventually leading to reactivation of HIV-1 in latently infected cells. Conclusion: Our observations indicate that periodontal diseases could act as a significant risk-factor for HIV-1 reactivation and might contribute to the systemic dissemination of the virus. Because this could result in the clinical progression of AIDS, the essential role of maintaining oral hygiene and controlling oral diseases is warranted in prevention of AIDS progression. This study was supported by Grant from Dental Research Center, Nihon University School of Dentistry.