title: Anx2 interacts with HIV-1 Gag at phosphatidylinositol (4,5) bisphosphate-containing lipid rafts and increases viral production in 293T cells.
abstract: The neuronal damage characteristic of HIV-1-mediated CNS diseases is inflicted by HIV-1 infected brain macrophages. Several steps of viral replication, including assembly and budding, differ between macrophages and T cells; it is likely that cell-specific host factors mediate these differences. We previously defined Annexin 2 (Anx2) as an HIV Gag binding partner in human monocyte-derived macrophages (MDMs) that promotes proper viral assembly. Anx2, a calcium-dependent membrane-binding protein that can aggregate phospholipid-containing lipid rafts, is expressed to high levels in macrophages, but not in T lymphocytes or the 293T cell line. Here, we use bimolecular fluorescence complementation in the 293T cell model to demonstrate that Anx2 and HIV-1 Gag interact at the phosphatidylinositol (4,5) bisphosphate-containing lipid raft membrane domains at which Gag mediates viral assembly. Furthermore, we demonstrate that Anx2 expression in 293T cells increases Gag processing and HIV-1 production. These data provide new evidence that Anx2, by interacting with Gag at the membranes that support viral assembly, functions in the late stages of HIV-1 replication.
authors.affiliation: Department of Neurology and Microbiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Alexia V
authors.initials: AV
authors.lastname: Harrist
authors.forename: Elena V
authors.initials: EV
authors.lastname: Ryzhova
authors.forename: Thomas
authors.initials: T
authors.lastname: Harvey
authors.forename: Francisco
authors.initials: F
authors.lastname: González-Scarano