Gp41 dynamically interacts with the TCR in the immune synapse and promotes early T cell activation

Oren Yakovian, Roland Schwarzer, Julia Sajman, Yair Neve-Oz, Yair Razvag, Andreas Herrmann, Eilon Sherman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The HIV-1 glycoprotein gp41 critically mediates CD4+ T-cell infection by HIV-1 during viral entry, assembly, and release. Although multiple immune-regulatory activities of gp41 have been reported, the underlying mechanisms of these activities remain poorly understood. Here we employed multi-colour single molecule localization microscopy (SMLM) to resolve interactions of gp41 proteins with cellular proteins at the plasma membrane (PM) of fixed and live CD4+ T-cells with resolution of ~20-30 nm. We observed that gp41 clusters dynamically associated with the T cell antigen receptor (TCR) at the immune synapse upon TCR stimulation. This interaction, confirmed by FRET, depended on the virus clone, was reduced by the gp41 ectodomain in tight contacts, and was completely abrogated by mutation of the gp41 transmembrane domain. Strikingly, gp41 preferentially colocalized with phosphorylated TCRs at the PM of activated T-cells and promoted TCR phosphorylation. Gp41 expression also resulted in enhanced CD69 upregulation, and in massive cell death after 24-48 hrs. Our results shed new light on HIV-1 assembly mechanisms at the PM of host T-cells and its impact on TCR stimulation.

Original languageAmerican English
Article number9747
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2018

Bibliographical note

Funding Information:
The authors would like to thank Prof. Yechiel Shai (The Weizmann Institute) and members of his group for multiple discussions and assistance with the gp41(HXB2) constructs, and Dr. Naomi Melamed-Book (The Bio-imaging unit at the Silberman Institute for life-sciences of the Hebrew University) for assistance with confocal imaging. This research was supported by Grant no. 321993 from the Marie Skłodowska-Curie actions of the European Commission, the HU-HUJI fund for collaborative research, and Grants no. 1417/13 and no. 1937/13 from the Israeli Science Foundation and Deutsche Forschungsgemeinschaft SFB 740.

Publisher Copyright:
© 2018 The Author(s).

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