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ZAP‐70 kinase regulates HIV cell‐to‐cell spread and virological synapse formation
Author(s) -
SolFoulon Nathalie,
Sourisseau Marion,
Porrot Françoise,
Thoulouze MariaIsabel,
Trouillet Céline,
Nobile Cinzia,
Blanchet Fabien,
di Bartolo Vincenzo,
Noraz Nelly,
Taylor Naomi,
Alcover Andres,
Hivroz Claire,
Schwartz Olivier
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601509
Subject(s) - biology , microbiology and biotechnology , immunological synapse , intracellular , viral replication , cell , virology , t cell , synapse , kinase , virus , immunology , genetics , immune system , neuroscience , t cell receptor
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.