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Journal of Virology, June 2009, p. 6234-6246, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.00282-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Simultaneous Cell-to-Cell Transmission of Human Immunodeficiency Virus to Multiple Targets through Polysynapses{triangledown} ,{dagger}

Dominika Rudnicka,1 Jérôme Feldmann,1 Françoise Porrot,1 Steve Wietgrefe,2 Stéphanie Guadagnini,3 Marie-Christine Prévost,3 Jérôme Estaquier,4 Ashley T. Haase,2 Nathalie Sol-Foulon,1*,{ddagger} and Olivier Schwartz1*,{ddagger}

Virus and Immunity Unit, Department of Virology, Institut Pasteur, URA CNRS 3015, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France,1 Department of Microbiology, University of Minnesota Medical School, MMC 196, 420 Delaware Street Southeast, Minneapolis, Minnesota 55455,2 Electron Microscopy Core Facility, Institut Pasteur, Paris, France,3 INSERM U841, Faculté de Médecine Henri Mondor, 8 rue du Général Sarrail, 94010 Créteil, France4

Received 9 February 2009/ Accepted 2 April 2009

Human immunodeficiency virus type 1 (HIV-1) efficiently propagates through cell-to-cell contacts, which include virological synapses (VS), filopodia, and nanotubes. Here, we quantified and characterized further these diverse modes of contact in lymphocytes. We report that viral transmission mainly occurs across VS and through "polysynapses," a rosette-like structure formed between one infected cell and multiple adjacent recipients. Polysynapses are characterized by simultaneous HIV clustering and transfer at multiple membrane regions. HIV Gag proteins often adopt a ring-like supramolecular organization at sites of intercellular contacts and colocalize with CD63 tetraspanin and raft components GM1, Thy-1, and CD59. In donor cells engaged in polysynapses, there is no preferential accumulation of Gag proteins at contact sites facing the microtubule organizing center. The LFA-1 adhesion molecule, known to facilitate viral replication, enhances formation of polysynapses. Altogether, our results reveal an underestimated mode of viral transfer through polysynapses. In HIV-infected individuals, these structures, by promoting concomitant infection of multiple targets in the vicinity of infected cells, may facilitate exponential viral growth and escape from immune responses.

* Corresponding author. Mailing address: Virus and Immunity Unit, Department of Virology, Institut Pasteur, URA CNRS 3015, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone for N.S.-F.: 331 45688783. Fax: 331 40613465. E-mail: natsol{at}pasteur.fr. Phone for O.S.: Phone: 331 45688353. Fax: 331 40613465. E-mail: schwartz{at}pasteur.fr

{triangledown} Published ahead of print on 15 April 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} N.S.-F. and O.S. contributed equally to this work.

Journal of Virology, June 2009, p. 6234-6246, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.00282-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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