Human herpesvirus 8-encoded chemokine vCCL2/vMIP-II is an agonist of the atypical chemokine receptor ACKR3/CXCR7

Martyna Szpakowska, Nadine Dupuis, Alessandra Baragli, Manuel Counson, Julien Hanson, Jacques Piette, Andy Chevigné*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

Abstract

The atypical chemokine receptor CXCR7/ACKR3 binds two endogenous chemokines, CXCL12 and CXCL11, and is upregulated in many cancers or following infection by several cancer-inducing viruses, including HHV-8. ACKR3 is a ligand-scavenging receptor and does not activate the canonical G protein pathways but was proposed to trigger β-arrestin-dependent signaling. Here, we identified the human herpesvirus 8-encoded CC chemokine vCCL2/vMIP-II as a third high-affinity ligand for ACKR3. vCCL2 acted as partial ACKR3 agonist, inducing β-arrestin recruitment to the receptor, subsequent reduction of its surface levels and its delivery to endosomes. In addition, ACKR3 reduced vCCL2-triggered MAP kinase and PI3K/Akt signaling through other chemokine receptors. Our data suggest that ACKR3 acts as a scavenger receptor for vCCL2, regulating its availability and activity toward human receptors, thereby likely controlling its function in HHV-8 infection. Our study provides new insights into the complex crosstalk between viral chemokines and host receptors as well as into the biology of ACKR3, this atypical and still enigmatic receptor.

Original languageEnglish
Pages (from-to)14-21
Number of pages8
JournalBiochemical Pharmacology
Volume114
DOIs
Publication statusPublished - 15 Aug 2016

Keywords

  • ACKR3
  • CXCR7
  • HHV-8
  • Kaposi's sarcoma
  • vCCL2
  • vMIP-II

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