fermer

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

Sol-Foulon, N.; Sourisseau, M.; Porrot, F.; Thoulouze, M. I.; Trouillet, C.; Nobile, C.; Blanchet, F.; di Bartolo, V.; Noraz, N.; Taylor, N.; Alcover, A.; Hivroz, C.; Schwartz, O.

Embo Journal

2007-01-24 / vol 26 / pages 516-526

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 kinasedead 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.

0261-4189

Étiquettes

activation; antigen receptor; tyrosine kinase; human-immunodeficiency-virus; immune synapse; immunological synapse; adapter protein; dendritic cells; hiv; transmission; type-1 infection; virological synapse; zap-70

Toutes les publications