Histone deacetylase 6 regulates human immunodeficiency virus type 1 infection.
Valenzuela-Fernández A,
Alvarez S,
Gordon-Alonso M,
Barrero M,
Ursa A,
Cabrero JR,
Fernández G,
Naranjo-Suárez S,
Yáñez-Mo M,
Serrador JM,
Muñoz-Fernández MA,
Sánchez-Madrid F.
Servicio de Inmunología, Hospital Universitario de La Princesa, 28006 Madrid, Spain.
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.
PMID: 16148047 [PubMed - indexed for MEDLINE]
PMCID: PMC1266439