Syracuse

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

Archive ouverte

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

Edité par CCSD ; EMBO Press -

International audience. 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.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion