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 Hildreth, Xinhong Dong

Research output: Contribution to journalArticle

27 Scopus citations

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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    Cooper, J., Liu, L., Woodruff, E. A., Taylor, H. E., Goodwin, J. S., D'Aquila, R. T., Spearman, P., Hildreth, J., & Dong, X. (2011). Filamin A protein interacts with human immunodeficiency virus type 1 Gag protein and contributes to productive particle assembly. Journal of Biological Chemistry, 286(32), 28498-28510. https://doi.org/10.1074/jbc.M111.239053