Filamin A protein interacts with human immunodeficiency virus type 1 Gag protein and contributes to productive particle assembly

JoAnn Cooper, Ling Liu, Elvin A. Woodruff, Harry E. Taylor, J. Shawn Goodwin, Richard T. D'Aquila, Paul Spearman, James E K Hildreth, Xinhong Dong

Research output: Contribution to journalArticlepeer-review

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 filaminAregulates 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 filaminAis involved in the distinct step of the Gag trafficking pathway. The discovery of the Gag-filaminAinteraction may provide a new therapeutic target for the treatment of HIV infection.

Original languageEnglish (US)
Pages (from-to)28498-28510
Number of pages13
JournalJournal of Biological Chemistry
Volume286
Issue number32
DOIs
StatePublished - Aug 12 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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