ZAP-70 Kinase Regulates HIV Cell-to-cell Spread and Virological Synapse Formation
Overview
Molecular Biology
Authors
Affiliations
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.
Avalos B, Kulbe J, Ford M, Laird A, Walter K, Mante M Viruses. 2024; 16(10.
PMID: 39459844 PMC: 11512329. DOI: 10.3390/v16101509.
HIV Infection: Shaping the Complex, Dynamic, and Interconnected Network of the Cytoskeleton.
Cabrera-Rodriguez R, Perez-Yanes S, Lorenzo-Sanchez I, Trujillo-Gonzalez R, Estevez-Herrera J, Garcia-Luis J Int J Mol Sci. 2023; 24(17).
PMID: 37685911 PMC: 10487602. DOI: 10.3390/ijms241713104.
Th17 CD4+ T-Cell as a Preferential Target for HIV Reservoirs.
Renault C, Veyrenche N, Mennechet F, Bedin A, Routy J, Van de Perre P Front Immunol. 2022; 13:822576.
PMID: 35197986 PMC: 8858966. DOI: 10.3389/fimmu.2022.822576.
Reif T, Dyckhoff G, Hohenberger R, Kolbe C, Gruell H, Klein F Cell Rep Med. 2021; 2(6):100317.
PMID: 34195682 PMC: 8233696. DOI: 10.1016/j.xcrm.2021.100317.
Ma L, Zhang H, Zhang Y, Li H, An M, Zhao B J Transl Med. 2021; 19(1):135.
PMID: 33794921 PMC: 8015739. DOI: 10.1186/s12967-021-02802-9.