HCMV vCXCL1 Binds Several Chemokine Receptors and Preferentially Attracts Neutrophils over NK Cells by Interacting with CXCR2

Rachel Yamin, Laura S.M. Lecker, Yiska Weisblum, Alon Vitenshtein, Vu Thuy Khanh Le-Trilling, Dana G. Wolf, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

HCMV is a highly sophisticated virus that has developed various mechanisms for immune evasion and viral dissemination throughout the body (partially mediated by neutrophils). NK cells play an important role in elimination of HCMV-infected cells. Both neutrophils and NK cells utilize similar sets of chemokine receptors to traffic, to and from, various organs. However, the mechanisms by which HCMV attracts neutrophils and not NK cells are largely unknown. Here, we show a unique viral protein, vCXCL1, which targets three chemokine receptors: CXCR1 and CXCR2 expressed on neutrophils and CXCR1 and CX3CR1 expressed on NK cells. Although vCXCL1 attracted both cell types, neutrophils migrated faster and more efficiently than NK cells through the binding of CXCR2. Therefore, we propose that HCMV has developed vCXCL1 to orchestrate its rapid systemic dissemination through preferential attraction of neutrophils and uses alternative mechanisms to counteract the later attraction of NK cells.

Original languageAmerican English
Pages (from-to)1542-1553
Number of pages12
JournalCell Reports
Volume15
Issue number7
DOIs
StatePublished - 17 May 2016

Bibliographical note

Funding Information:
This study was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement number 320473-BacNK. Further support came from the I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation and by the I-Core on Chromatin and RNA in Gene Regulation, the GIF foundation, the Lewis family foundation, the ICRF professorship grant, the Israeli Science Foundation, the Helmholtz Israel grant, and the Rosetrees Trust (all to O.M.). This work was also supported by grants from the Israel Science Foundation (grant number 275/13); the Israeli Ministry of Health (grant number 10998); the European Union Seventh Framework Programme 562 FP7/2012-2016 (grant agreement number 316655); and the Samueli Institute Brain Mind & Healing Center, under a contract from the US Army Medical Research and Materiel Command (USAMRAA award no. W81XWH-10-1-0938), within the TATRC portfolio of Integrative Medicine Research. O.M. is a Crown Professor of Molecular Immunology.

Publisher Copyright:
© 2016 The Author(s).

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