@article{5b734793375f4494b413fb6cc4681065,
title = "Human herpesvirus 8-encoded chemokine vCCL2/vMIP-II is an agonist of the atypical chemokine receptor ACKR3/CXCR7",
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.",
keywords = "ACKR3, CXCR7, HHV-8, Kaposi's sarcoma, vCCL2, vMIP-II",
author = "Martyna Szpakowska and Nadine Dupuis and Alessandra Baragli and Manuel Counson and Julien Hanson and Jacques Piette and Andy Chevign{\'e}",
note = "Funding Information: This study was supported by the Luxembourg Institute of Health (LIH), MESR grants 20100708 and 20150415 , the “Fonds National de la Recherche” ( FNR , Luxembourg), grants AFR-3004509 , F.R.S.-FNRS-T{\'e}l{\'e}vie grants 7456814 and 7461515 as well as F.R.S.-FNRS incentive grant for scientific research ( MIS-F.4510.14 ). Martyna Szpakowska is an “Aides {\`a} la Formation-Recherche” (AFR-FNR, Luxembourg) PhD fellow. Julien Hanson is a “Fonds de la Recherche Scientifique (F.R.S.-FNRS, Belgium)” research associate. Nadine Dupuis is a “Fonds pour la Recherche dans l{\textquoteright}Industrie et l{\textquoteright}Agriculture (FRIA, Belgium)” research fellow. The authors wish to thank Danielle Perez Bercoff and Claude P. Muller for fruitful discussions and critical reading of the manuscript, Dominique Schols and Thomas D{\textquoteright}huys for their support in calcium measurement experiments and Nadia Beaupain for arrestin recruitment experiments. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = aug,
day = "15",
doi = "10.1016/j.bcp.2016.05.012",
language = "English",
volume = "114",
pages = "14--21",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
}