ZAP-70 kinase regulates HIV cell-to-cell spread and virological synapse formation.
EMBO J
; 26(2): 516-26, 2007 Jan 24.
Article
em En
| MEDLINE
| ID: mdl-17215865
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Comunicação Celular
/
HIV
/
Proteína-Tirosina Quinase ZAP-70
Limite:
Humans
/
Infant
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article