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Journal of Virology, March 2006, p. 2949-2957, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2949-2957.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Infection of Dendritic Cells (DCs), Not DC-SIGN-Mediated Internalization of Human Immunodeficiency Virus, Is Required for Long-Term Transfer of Virus to T Cells

Laura Burleigh,¹ Pierre-Yves Lozach,^1,5 Cécile Schiffer,² Isabelle Staropoli,¹ Valérie Pezo,^3, Françoise Porrot,⁴ Bruno Canque,² Jean-Louis Virelizier,¹ Fernando Arenzana-Seisdedos,¹ and Ali Amara^1*

Unité d'Immunologie Virale,¹ Groupe Virus et Immunité, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris, France,⁴ CNRS UMR 7151 IUH, Centre Hayem, Hôpital Saint Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France,² Institut Curie INSERM U520, 12 rue Lhomond, 75005 Paris, France,³ UMR de Virologie Moléculaire et Structurale, CNRS 2472-INRA 1157, Bât. 14B, 1 avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France⁵

Received 31 October 2005/ Accepted 27 December 2005

The C-type lectin DC-SIGN expressed on immature dendritic cells (DCs) captures human immunodeficiency virus (HIV) particles and enhances the infection of CD4⁺ T cells. This process, known as trans-enhancement of T-cell infection, has been related to HIV endocytosis. It has been proposed that DC-SIGN targets HIV to a nondegradative compartment within DCs and DC-SIGN-expressing cells, allowing incoming virus to persist for several days before infecting target cells. In this study, we provide several lines of evidence suggesting that intracellular storage of intact virions does not contribute to HIV transmission. We show that endocytosis-defective DC-SIGN molecules enhance T-cell infection as efficiently as their wild-type counterparts, indicating that DC-SIGN-mediated HIV internalization is dispensable for trans-enhancement. Furthermore, using immature DCs that are genetically resistant to infection, we demonstrate that several days after viral uptake, HIV transfer from DCs to T cells requires viral fusion and occurs exclusively through DC infection and transmission of newly synthesized viral particles. Importantly, our results suggest that DC-SIGN participates in this process by cooperating with the HIV entry receptors to facilitate cis-infection of immature DCs and subsequent viral transfer to T cells. We suggest that such a mechanism, rather than intracellular storage of incoming virus, accounts for the long-term transfer of HIV to CD4⁺ T cells and may contribute to the spread of infection by DCs.

Present address: Génoscope 2, rue Gaston Crémieux, 91000 Evry, France.

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