Histone deacetylase 6 regulates human immunodeficiency virus type 1 infection.
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.
Valenzuela-Fernández
Agustín
A
Servicio de Inmunología, Hospital Universitario de La Princesa, 28006 Madrid, Spain.
Alvarez
Susana
S
Gordon-Alonso
Mónica
M
Barrero
Marta
M
Ursa
Angeles
A
Cabrero
J Román
JR
Fernández
Gerónimo
G
Naranjo-Suárez
Salvador
S
Yáñez-Mo
Maria
M
Serrador
Juan M
JM
Muñoz-Fernández
M Angeles
MA
Sánchez-Madrid
Francisco
F
D000107:Acetylation / Q000187:drug effects; D062365:Aminobenzoates / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002459:Cell Fusion; D045744:Cell Line, Tumor; D020868:Gene Silencing / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015658:HIV Infections / Q000097:blood / Q000378:metabolism*; D015497:HIV-1; D006367:HeLa Cells; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D019169:Jurkat Cells; D011719:Pyrazines / Q000494:pharmacology; D012342:RNA, Small Nuclear; D014162:Transfection; D014404:Tubulin / Q000378:metabolism
C477641:3-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; D062365:Aminobenzoates; D015699:HIV Envelope Protein gp120; D006877:Hydroxamic Acids; D011719:Pyrazines; D012342:RNA, Small Nuclear; D014404:Tubulin; C012589:trichostatin A; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases