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

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.
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Submitted on : Thursday, September 24, 2020 - 9:26:02 AM
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Nathalie Sol-Foulon, Marion Sourisseau, Françoise Porrot, Maria-Isabel Thoulouze, Céline Trouillet, et al.. ZAP-70 kinase regulates HIV cell-to-cell spread and virological synapse formation.. EMBO Journal, EMBO Press, 2007, 26 (2), pp.516-26. ⟨10.1038/sj.emboj.7601509⟩. ⟨pasteur-00292789⟩

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