Analysis of human immunodeficiency virus type 1 matrix binding to membranes and nucleic acids

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Abstract

The human immunodeficiency virus type 1 (HIV-1) matrix (MA) protein targets HIV-1 precursor Gag (PrGag) proteins to assembly sites at plasma membrane (PM) sites that are enriched in cholesterol and phosphatidylinositol-(4,5)- bisphosphate [PI(4,5)P2]. MA is myristoylated, which enhances membrane binding, and specifically binds PI(4,5)P2 through headgroup and 2′ acyl chain contacts. MA also binds nucleic acids, although the significance of this association with regard to the viral life cycle is unclear. We have devised a novel MA binding assay and used it to examine MA interactions with membranes and nucleic acids. Our results indicate that cholesterol increases the selectivity of MA for PI(4,5)P2-containing membranes, that PI(4,5)P2 binding tolerates 2′ acyl chain variation, and that the MA myristate enhances membrane binding efficiency but not selectivity. We also observed that soluble PI(4,5)P2 analogues do not compete effectively with PI(4,5)P2-containing liposomes for MA binding but surprisingly do increase nonspecific binding to liposomes. Finally, we have demonstrated that PI(4,5)P2-containing liposomes successfully outcompete nucleic acids for MA binding, whereas other liposomes do not. These results support a model in which RNA binding protects MA from associating with inappropriate cellular membranes prior to PrGag delivery to PM assembly sites.

Original languageEnglish (US)
Pages (from-to)12196-12203
Number of pages8
JournalJournal of Virology
Volume83
Issue number23
DOIs
StatePublished - Dec 2009

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Human immunodeficiency virus 1
Nucleic Acids
nucleic acids
HIV-1
Liposomes
Membranes
plasma membrane
cholesterol
phosphatidylinositols
Cholesterol
Cell Membrane
gag Gene Products
proteins
RNA
Myristic Acid
Phosphatidylinositols
Life Cycle Stages
assays

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Analysis of human immunodeficiency virus type 1 matrix binding to membranes and nucleic acids. / Alfadhli, Ayna; Still, Amelia; Barklis, Eric.

In: Journal of Virology, Vol. 83, No. 23, 12.2009, p. 12196-12203.

Research output: Contribution to journalArticle

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