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Journal of Virology, March 2006, p. 2694-2704, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2694-2704.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Annexin 2: a Novel Human Immunodeficiency Virus Type 1 Gag Binding Protein Involved in Replication in Monocyte-Derived Macrophages

Elena V. Ryzhova,{dagger} Robin M. Vos,{dagger},{ddagger} Andrew V. Albright, Alexia V. Harrist, Thomas Harvey, and Francisco González-Scarano*

Departments of Neurology and Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania

Received 9 September 2005/ Accepted 15 December 2005

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.

* Corresponding author. Mailing address: Department of Neurology, University of Pennsylvania, 3 W. Gates, 3400 Spruce Street, Philadelphia, PA 19104-4283. Phone: (215) 662-3360. Fax: (215) 662-3362. E-mail: scarano{at}mail.med.upenn.edu.

{dagger} These authors contributed equally to this work.

{ddagger} Present address: Department of Pathology, Harvard Medical School, Boston, MA 02115.

Journal of Virology, March 2006, p. 2694-2704, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2694-2704.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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