ZAP-70 kinase regulates HIV cell-to-cell spread and virological synapse formation.
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.
Sol-Foulon
Nathalie
N
Groupe Virus et Immunité, Institut Pasteur, CNRS URA1930, France.
Sourisseau
Marion
M
Porrot
Françoise
F
Thoulouze
Maria-Isabel
MI
Trouillet
Céline
C
Nobile
Cinzia
C
Blanchet
Fabien
F
di Bartolo
Vincenzo
V
Noraz
Nelly
N
Taylor
Naomi
N
Alcover
Andres
A
Hivroz
Claire
C
Schwartz
Olivier
O
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*
D051746:ZAP-70 Protein-Tyrosine Kinase