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

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• 作者：Martyna Szpakowska^a ; ^{martyna.szpakowska@lih.lu" class="auth_mail" title="E-mail the corresponding author} ; Nadine Dupuis^b ; ¹ ; ^{ndupuis@ulg.ac.be" class="auth_mail" title="E-mail the corresponding author} ; Alessandra Baragli^a ; ¹ ; ^{alessandra.baragli@lih.lu" class="auth_mail" title="E-mail the corresponding author} ; Manuel Counson^a ; ^{manuel.counson@lih.lu" class="auth_mail" title="E-mail the corresponding author} ; Julien Hanson^b ; ^{j.hanson@ulg.ac.be" class="auth_mail" title="E-mail the corresponding author} ; Jacques Piette^c ; ^{jpiette@ulg.ac.be" class="auth_mail" title="E-mail the corresponding author} ; Andy Chevigné ; ^a ; ^{andy.chevigne@lih.lu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ACKR ; atypical chemokine receptor ; CCKAR ; cholecystokinin A receptor ; CCL ; chemokine (CC motif) ligand ; CHO ; Chinese hamster ovary ; CXCL ; chemokine (CXC motif) ligand ; CX3CL ; chemokine (CX3C motif) ligand ; EBV ; Epstein&ndash ; Barr virus ; ERK ; extracellular receptor kinase ; GFP2 ; green fluorescent protein 2 ; GPCR ; G protein-coupled receptor ; HCMV ; human cytomegalovirus ; HEK ; human embryonic kidney ; HHV-8 ; human herpesvirus 8 ; HTLV-1 ; human T-cell leukemia virus 1 ; KS ; Kaposi&rsquo ; s sarcoma ; KSHV
• 刊名：Biochemical Pharmacology
• 出版年：2016
• 出版时间：15 August 2016
• 年：2016
• 卷：114
• 期：Complete
• 页码：14-21
• 全文大小：1709 K

文摘

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.