title: HCMV vCXCL1 Binds Several Chemokine Receptors and Preferentially Attracts Neutrophils over NK Cells by Interacting with CXCR2.
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.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Yamin
authors.affiliation: German Cancer Research Center, DKFZ, 69120 Heidelberg, Germany.
authors.forename: Laura S M
authors.initials: LSM
authors.lastname: Lecker
authors.affiliation: Clinical Virology Unit, Hadassah Hebrew University Medical Center and Department of Biochemistry and Chanock Center for Virology, IMRIC, Jerusalem 91120, Israel.
authors.forename: Yiska
authors.initials: Y
authors.lastname: Weisblum
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Vitenshtein
authors.affiliation: Institute for Virology of the University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Vu Thuy Khanh
authors.initials: VTK
authors.lastname: Le-Trilling
authors.affiliation: Clinical Virology Unit, Hadassah Hebrew University Medical Center and Department of Biochemistry and Chanock Center for Virology, IMRIC, Jerusalem 91120, Israel.
authors.forename: Dana G
authors.initials: DG
authors.lastname: Wolf
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel. Electronic address: oferm@ekmd.huji.ac.il.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D002465:Cell Movement; D054360:Chemokine CXCL1 / Q000378:metabolism; D003587:Cytomegalovirus / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000378:metabolism / Q000821:virology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D008024:Ligands; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D054360:Chemokine CXCL1; D008024:Ligands; D019707:Receptors, Chemokine; D023063:Receptors, Interleukin-8B