Annexin 2: a novel human immunodeficiency virus type 1 Gag binding protein involved in replication in monocyte-derived macrophages.
Human immunodeficiency virus (HIV) replication in the major natural target cells, CD4+ T lymphocytes and macrophages, is parallel in many aspects of the virus life cycle. However, it differs as to viral assembly and budding, which take place on plasma membranes in T cells and on endosomal membranes in macrophages. It has been postulated that cell type-specific host factors may aid in directing viral assembly to distinct destinations. In this study we defined annexin 2 (Anx2) as a novel HIV Gag binding partner in macrophages. Anx2-Gag binding was confined to productively infected macrophages and was not detected in quiescently infected monocyte-derived macrophages (MDM) in which an HIV replication block was mapped to the late stages of the viral life cycle (A. V. Albright, R. M. Vos, and F. Gonzalez-Scarano, Virology 325:328-339, 2004). We demonstrate that the Anx2-Gag interaction likely occurs at the limiting membranes of late endosomes/multivesicular bodies and that Anx2 depletion is associated with a significant decline in the infectivity of released virions; this coincided with incomplete Gag processing and inefficient incorporation of CD63. Cumulatively, our data suggest that Anx2 is essential for the proper assembly of HIV in MDM.
Ryzhova
Elena V
EV
Department of Neurology and Microbiology, University of Pennsylvania, 3 W. Gates, 3400 Spruce Street, Philadelphia, Pennsylvania 19104-4283, USA.
Vos
Robin M
RM
Albright
Andrew V
AV
Harrist
Alexia V
AV
Harvey
Thomas
T
González-Scarano
Francisco
F
D017306:Annexin A2 / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D002478:Cells, Cultured; D015683:Gene Products, gag / Q000378:metabolism*; D015750:Genes, gag; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D060149:Tetraspanin 30; D019065:Virus Assembly; D014779:Virus Replication
C472822:ANXA2 protein, human; D017306:Annexin A2; D015703:Antigens, CD; C554586:CD63 protein, human; D015683:Gene Products, gag; D010980:Platelet Membrane Glycoproteins; D011498:Protein Precursors; D060149:Tetraspanin 30; C059767:p55 gag precursor protein, Human immunodeficiency virus 1