Histone deacetylase 6 regulates human immunodeficiency virus type 1 infection

Mol Biol Cell. 2005 Nov;16(11):5445-54. doi: 10.1091/mbc.e05-04-0354. Epub 2005 Sep 7.

Abstract

Efficient human immunodeficiency virus (HIV)-1 infection depends on multiple interactions between the viral gp41/gp120 envelope (Env) proteins and cell surface receptors. However, cytoskeleton-associated proteins that modify membrane dynamics may also regulate the formation of the HIV-mediated fusion pore and hence viral infection. Because the effects of HDAC6-tubulin deacetylase on cortical alpha-tubulin regulate cell migration and immune synapse organization, we explored the possible role of HDAC6 in HIV-1-envelope-mediated cell fusion and infection. The binding of the gp120 protein to CD4+-permissive cells increased the level of acetylated alpha-tubulin in a CD4-dependent manner. Furthermore, overexpression of active HDAC6 inhibited the acetylation of alpha-tubulin, and remarkably, prevented HIV-1 envelope-dependent cell fusion and infection without affecting the expression and codistribution of HIV-1 receptors. In contrast, knockdown of HDAC6 expression or inhibition of its tubulin deacetylase activity strongly enhanced HIV-1 infection and syncytia formation. These results demonstrate that HDAC6 plays a significant role in regulating HIV-1 infection and Env-mediated syncytia formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Aminobenzoates / pharmacology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Fusion
  • Cell Line, Tumor
  • Gene Silencing / physiology
  • HIV Envelope Protein gp120 / physiology*
  • HIV Infections / blood
  • HIV Infections / metabolism*
  • HIV-1*
  • HeLa Cells
  • Histone Deacetylase 6
  • Histone Deacetylases / genetics
  • Histone Deacetylases / physiology*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Jurkat Cells
  • Pyrazines / pharmacology
  • RNA, Small Nuclear
  • Transfection
  • Tubulin / metabolism

Substances

  • 3-amino-5-(1-(2-((4-(amino(imino)methyl)benzyl)amino)-2-oxoethyl)-3-chloro-5-(isopropylamino)-6-oxo-1,6-dihydropyrazin-2-yl)benzoic acid
  • Aminobenzoates
  • HIV Envelope Protein gp120
  • Hydroxamic Acids
  • Pyrazines
  • RNA, Small Nuclear
  • Tubulin
  • trichostatin A
  • HDAC6 protein, human
  • Histone Deacetylase 6
  • Histone Deacetylases