» Articles » PMID: 17215865

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.

Citing Articles

Cannabis Use and Cannabidiol Modulate HIV-Induced Alterations in TREM2 Expression: Implications for Age-Related Neuropathogenesis.

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.


Contact-dependent inhibition of HIV-1 replication in human tonsil cultures by polymorphonuclear neutrophils.

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.


Integrated analysis of lncRNA, miRNA and mRNA profiles reveals potential lncRNA functions during early HIV infection.

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.


References
1.
Das V, Nal B, Dujeancourt A, Thoulouze M, Galli T, Roux P . Activation-induced polarized recycling targets T cell antigen receptors to the immunological synapse; involvement of SNARE complexes. Immunity. 2004; 20(5):577-88. DOI: 10.1016/s1074-7613(04)00106-2. View

2.
Griffith C, Zhang W, Wange R . ZAP-70-dependent and -independent activation of Erk in Jurkat T cells. Differences in signaling induced by H2o2 and Cd3 cross-linking. J Biol Chem. 1998; 273(17):10771-6. DOI: 10.1074/jbc.273.17.10771. View

3.
Noraz N, Schwarz K, Steinberg M, Dardalhon V, Rebouissou C, Hipskind R . Alternative antigen receptor (TCR) signaling in T cells derived from ZAP-70-deficient patients expressing high levels of Syk. J Biol Chem. 2000; 275(21):15832-8. DOI: 10.1074/jbc.M908568199. View

4.
Meinl E, Lengenfelder D, Blank N, Pirzer R, Barata L, Hivroz C . Differential requirement of ZAP-70 for CD2-mediated activation pathways of mature human T cells. J Immunol. 2000; 165(7):3578-83. DOI: 10.4049/jimmunol.165.7.3578. View

5.
Hioe C, Chien Jr P, Lu C, Springer T, Wang X, Bandres J . LFA-1 expression on target cells promotes human immunodeficiency virus type 1 infection and transmission. J Virol. 2001; 75(2):1077-82. PMC: 114007. DOI: 10.1128/JVI.75.2.1077-1082.2001. View