Anx2 interacts with HIV-1 Gag at phosphatidylinositol (4,5) bisphosphate-containing lipid rafts and increases viral production in 293T cells

Alexia V. Harrist, Elena V. Ryzhova, Thomas Harvey, Francisco González-Scarano

Research output: Contribution to journalArticle

28 Citations (Scopus)

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) bisphosphatecontaining 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.

Original languageEnglish (US)
Article numbere5020
JournalPLoS One
Volume4
Issue number3
DOIs
StatePublished - Mar 27 2009
Externally publishedYes

Fingerprint

Annexins
HEK293 Cells
phosphatidylinositols
Phosphatidylinositols
Human immunodeficiency virus 1
Macrophages
HIV-1
Virus Assembly
Lipids
macrophages
lipids
T-cells
cells
T-lymphocytes
Membranes
T-Lymphocytes
HIV-2
Central Nervous System Diseases
cell aggregates
Membrane Lipids

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Anx2 interacts with HIV-1 Gag at phosphatidylinositol (4,5) bisphosphate-containing lipid rafts and increases viral production in 293T cells. / Harrist, Alexia V.; Ryzhova, Elena V.; Harvey, Thomas; González-Scarano, Francisco.

In: PLoS One, Vol. 4, No. 3, e5020, 27.03.2009.

Research output: Contribution to journalArticle

Harrist, Alexia V. ; Ryzhova, Elena V. ; Harvey, Thomas ; González-Scarano, Francisco. / Anx2 interacts with HIV-1 Gag at phosphatidylinositol (4,5) bisphosphate-containing lipid rafts and increases viral production in 293T cells. In: PLoS One. 2009 ; Vol. 4, No. 3.
@article{f9bf54f6e54e41989a4ba77b598fd8e9,
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) bisphosphatecontaining 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.",
author = "Harrist, {Alexia V.} and Ryzhova, {Elena V.} and Thomas Harvey and Francisco Gonz{\'a}lez-Scarano",
year = "2009",
month = "3",
day = "27",
doi = "10.1371/journal.pone.0005020",
language = "English (US)",
volume = "4",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Anx2 interacts with HIV-1 Gag at phosphatidylinositol (4,5) bisphosphate-containing lipid rafts and increases viral production in 293T cells

AU - Harrist, Alexia V.

AU - Ryzhova, Elena V.

AU - Harvey, Thomas

AU - González-Scarano, Francisco

PY - 2009/3/27

Y1 - 2009/3/27

N2 - 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) bisphosphatecontaining 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.

AB - 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) bisphosphatecontaining 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.

UR - http://www.scopus.com/inward/record.url?scp=63449114891&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63449114891&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0005020

DO - 10.1371/journal.pone.0005020

M3 - Article

C2 - 19325895

AN - SCOPUS:63449114891

VL - 4

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e5020

ER -