title: Filamin A protein interacts with human immunodeficiency virus type 1 Gag protein and contributes to productive particle assembly.
abstract: HIV-1 Gag precursor directs virus particle assembly and release. In a search for Gag-interacting proteins that are involved in late stages of the HIV-1 replication cycle, we performed yeast two-hybrid screening against a human cDNA library and identified the non-muscle actin filament cross-linking protein filamin A as a novel Gag binding partner. The 280-kDa filamin A regulates cortical actin network dynamics and participates in the anchoring of membrane proteins to the actin cytoskeleton. Recent studies have shown that filamin A facilitates HIV-1 cell-to-cell transmission by binding to HIV receptors and coreceptors and regulating their clustering on the target cell surface. Here we report a novel role for filamin A in HIV-1 Gag intracellular trafficking. We demonstrate that filamin A interacts with the capsid domain of HIV-1 Gag and that this interaction is involved in particle release in a productive manner. Disruption of this interaction eliminated Gag localization at the plasma membrane and induced Gag accumulation within internal compartments. Moreover, blocking clathrin-dependent endocytic pathways did not relieve the restriction to particle release induced by filamin A depletion. These results suggest that filamin A is involved in the distinct step of the Gag trafficking pathway. The discovery of the Gag-filamin A interaction may provide a new therapeutic target for the treatment of HIV infection.
authors.affiliation: Center for AIDS Health Disparities Research, Department of Microbiology, and Immunology, Meharry Medical College, Nashville, Tennessee 37208, USA.
authors.forename: JoAnn
authors.initials: J
authors.lastname: Cooper
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Elvin A
authors.initials: EA
authors.lastname: Woodruff
authors.forename: Harry E
authors.initials: HE
authors.lastname: Taylor
authors.forename: J Shawn
authors.initials: JS
authors.lastname: Goodwin
authors.forename: Richard T
authors.initials: RT
authors.lastname: D'Aquila
authors.forename: Paul
authors.initials: P
authors.lastname: Spearman
authors.forename: James E K
authors.initials: JE
authors.lastname: Hildreth
authors.forename: Xinhong
authors.initials: X
authors.lastname: Dong
mesh_terms: D002966:Clathrin / Q000235:genetics / Q000378:metabolism; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics; D064448:Filamins; D015723:Gene Library; D015658:HIV Infections / Q000235:genetics / Q000401:mortality* / Q000635:transmission; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics; D012441:Saccharomyces cerevisiae; D020798:Two-Hybrid System Techniques; D019065:Virus Assembly / Q000187:drug effects / Q000502:physiology*; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D002966:Clathrin; D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus