Article
- The EMBO Journal (2007) 26, 516 - 526
- doi:10.1038/sj.emboj.7601509
Published online: 11 January 2007
Subject Categories:
ZAP-70 kinase regulates HIV cell-to-cell spread and virological synapse formation
Nathalie Sol-Foulon1,a, Marion Sourisseau1,a, Françoise Porrot1, Maria-Isabel Thoulouze2, Céline Trouillet1, Cinzia Nobile3, Fabien Blanchet1, Vincenzo di Bartolo2, Nelly Noraz4, Naomi Taylor4, Andres Alcover2, Claire Hivroz3 and Olivier Schwartz1
- Groupe Virus et Immunité, Institut Pasteur, CNRS URA1930, France
- Unité de Biologie Cellulaire des Lymphocytes, Institut Pasteur, Paris, France
- INSERM Unité 653, Institut Curie, Paris, France
- CNRS UMR5535, Institut de Génétique Moléculaire, Montpellier, France
Correspondence to:
Olivier Schwartz, Virus and Immunity Group, Institut Pasteur, CNRS URA 1930, 28 rue du Dr Roux, 75724 Paris Cedex 15, France. Tel.: +33 1 45 68 83 53; fax: +33 1 45 68 89 40; E-mail: schwartz@pasteur.fr
aThese authors contributed equally to this work
Received 13 July 2006; Accepted 24 November 2006
Abstract
HIV efficiently spreads in lymphocytes, likely through virological synapses (VSs). These cell–cell junctions share some characteristics with immunological synapses, but cellular proteins required for their constitution remain poorly characterized. We have examined here the role of ZAP-70, a key kinase regulating T-cell activation and immunological synapse formation, in HIV replication. In lymphocytes deficient for ZAP-70, or expressing a kinase-dead mutant of the protein, HIV replication was strikingly delayed. We have characterized further this replication defect. ZAP-70 was dispensable for the early steps of viral cycle, from entry to expression of viral proteins. However, in the absence of ZAP-70, intracellular Gag localization was impaired. ZAP-70 was required in infected donor cells for efficient cell-to-cell HIV transmission to recipients and for formation of VSs. These results bring novel insights into the links that exist between T-cell activation and HIV spread, and suggest that HIV usurps components of the immunological synapse machinery to ensure its own spread through cell-to-cell contacts.
Keywords:
- HIV,
- virological synapse,
- ZAP-70
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