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The Journal of Immunology, 2006, 177: 5129-5137.
Copyright © 2006 by The American Association of Immunologists, Inc.

Tetraspanins CD9 and CD81 Modulate HIV-1-Induced Membrane Fusion1

Mónica Gordón-Alonso*, María Yañez-Mó*, Olga Barreiro*, Susana Álvarez{dagger}, M. Ángeles Muñoz-Fernández{dagger}, Agustín Valenzuela-Fernández2,* and Francisco Sánchez-Madrid3,*

* Servicio de Inmunología, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain; and {dagger} Departamento de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain

Protein organization on the membrane of target cells may modulate HIV-1 transmission. Since the tetraspanin CD81 is associated to CD4, the receptor of HIV-1 envelope protein (Env; gp120/gp41), we have explored the possibility that this molecule may modulate the initial steps of HIV-1 infection. On the other hand, CD81 belongs to the tetraspanin family, which has been described as organizers of protein microdomains on the plasma membrane. Therefore, the role of CD81 and other related tetraspanin, CD9, on the cell-to-cell fusion process mediated by HIV-1 was studied. We found that anti-tetraspanin Abs enhanced the syncytia formation induced by HIV-1 envelope proteins and viral entry in human T lymphoblasts. In addition, anti-CD81 Abs triggered its clustering in patches, where CD4 and CXCR4 were included. Moreover, the knocking down of CD81 and CD9 expression resulted in an increase in syncytia formation and viral entry. Accordingly, overexpression of CD81 and CD9 rendered cells less susceptible to Env-mediated syncytia formation. These data indicate that CD9 and CD81 have an important role in membrane fusion induced by HIV-1 envelope.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 F.S.-M. is supported by Ministerio de Educación y Ciencia Grant BFU2005-08435/BMC, Fundación para la Investigación y Prevención del SIDA en España (FIPSE) Grants 36289/02 and 24508/05, Lilly Foundation, and "Ayuda a la Investigación Básica 2002 de la Fundación Juan March." A.V.-F. is supported by grants from FIPSE 24508/05 and PI050995 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo.

2 Current address: Departamento de Medicina Física y Farmacología, Facultad de Medicina, Universidad de La Laguna, 38071 Tenerife, Spain.

3 Address correspondence and reprint requests to Dr. Francisco Sánchez-Madrid. Servicio de Inmunología. Hospital Universitario de la Princesa. Diego de León 62, 28006 Madrid, Spain. E-mail address: fsanchez.hlpr{at}salud.madrid.org

4 Abbreviations used in this paper: Env, envelope viral protein; FIV, feline immunodeficiency virus; HTLV-1, human T cell leukemia virus type 1; LEL, large extracellular loop; siRNA, short interference RNA; X-gal, 5-bromo-4-chloro-3-indoyl-beta-D-galactopyranoside.




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