ZAP-70 kinase regulates HIV cell-to-cell spread and virological synapse formation

Nathalie Sol-Foulon, Marion Sourisseau, Françoise Porrot, Maria Isabel Thoulouze, Céline Trouillet, Cinzia Nobile, Fabien Blanchet, Vincenzo Di Bartolo, Nelly Noraz, Naomi Taylor, Andres Alcover, Claire Hivroz, Olivier Schwartz

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

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.

Original languageEnglish
Pages (from-to)516-526
Number of pages11
JournalEMBO Journal
Volume26
Issue number2
DOIs
StatePublished - 24 Jan 2007
Externally publishedYes

Keywords

  • HIV
  • Virological synapse
  • ZAP-70

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