Cellular and Molecular Life Sciences

, Volume 69, Issue 15, pp 2583–2592

Reactivation of latent HIV-1 by a wide variety of butyric acid-producing bacteria

  • Kenichi Imai
  • Kiyoshi Yamada
  • Muneaki Tamura
  • Kuniyasu Ochiai
  • Takashi Okamoto
Research Article

DOI: 10.1007/s00018-012-0936-2

Cite this article as:
Imai, K., Yamada, K., Tamura, M. et al. Cell. Mol. Life Sci. (2012) 69: 2583. doi:10.1007/s00018-012-0936-2

Abstract

Latently infected cells harbor human immunodeficiency virus type 1 (HIV-1) proviral DNA copies integrated in heterochromatin, allowing persistence of transcriptionally silent proviruses. It is widely accepted that hypoacetylation of histone proteins by histone deacetylases (HDACs) is involved in maintaining the HIV-1 latency by repressing viral transcription. HIV-1 replication can be induced from latently infected cells by environmental factors, such as inflammation and co-infection with other microbes. It is known that a bacterial metabolite butyric acid inhibits catalytic action of HDAC and induces transcription of silenced genes including HIV-1 provirus. There are a number of such bacteria in gut, vaginal, and oral cavities that produce butyric acid during their anaerobic glycolysis. Since these organs are known to be the major site of HIV-1 transmission and its replication, we explored a possibility that explosive viral replication in these organs could be ascribable to butyric acid produced from anaerobic resident bacteria. In this study, we demonstrate that the culture supernatant of various bacteria producing butyric acid could greatly reactivate the latently-infected HIV-1. These bacteria include Fusobacterium nucleatum (commonly present in oral cavity, and gut), Clostridium cochlearium, Eubacterium multiforme (gut), and Anaerococcus tetradius (vagina). We also clarified that butyric acid in these culture supernatants could induce histone acetylation and HIV-1 replication by inhibiting HDAC. Our observations indicate that butyric acid-producing bacteria could be involved in AIDS progression by reactivating the latent HIV provirus and, subsequently, by eliminating such bacterial infection may contribute to the prevention of the AIDS development and transmission.

Keywords

HIV-1HDACEpigeneticsButyric acidHistone

Abbreviations

AIDS

Acquired immunodeficiency syndrome

ChIP

Chromatin immunoprecipitation

HDAC

Histone deacetylases

HIV-1

Human immunodeficiency virus type 1

LTR

Long terminal repeat

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Kenichi Imai
    • 1
    • 2
  • Kiyoshi Yamada
    • 2
  • Muneaki Tamura
    • 2
  • Kuniyasu Ochiai
    • 2
  • Takashi Okamoto
    • 1
  1. 1.Department of Molecular and Cellular BiologyNagoya City University Graduate School of Medical SciencesNagoyaJapan
  2. 2.Department of Microbiology, Division of Immunology and Pathobiology, Dental Research CenterNihon University School of DentistryChiyoda-kuJapan