title: 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.
authors.affiliation: Groupe Virus et Immunité, Institut Pasteur, CNRS URA1930, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sol-Foulon
authors.forename: Marion
authors.initials: M
authors.lastname: Sourisseau
authors.forename: Françoise
authors.initials: F
authors.lastname: Porrot
authors.forename: Maria-Isabel
authors.initials: MI
authors.lastname: Thoulouze
authors.forename: Céline
authors.initials: C
authors.lastname: Trouillet
authors.forename: Cinzia
authors.initials: C
authors.lastname: Nobile
authors.forename: Fabien
authors.initials: F
authors.lastname: Blanchet
authors.forename: Vincenzo
authors.initials: V
authors.lastname: di Bartolo
authors.forename: Nelly
authors.initials: N
authors.lastname: Noraz
authors.forename: Naomi
authors.initials: N
authors.lastname: Taylor
authors.forename: Andres
authors.initials: A
authors.lastname: Alcover
authors.forename: Claire
authors.initials: C
authors.lastname: Hivroz
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
mesh_terms: D002450:Cell Communication; D002478:Cells, Cultured; D006678:HIV / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007223:Infant; D019169:Jurkat Cells; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology*; D014779:Virus Replication; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000502:physiology*
chemical_list: D051746:ZAP-70 Protein-Tyrosine Kinase