title: Cytomegalovirus hijacks CX3CR1(hi) patrolling monocytes as immune-privileged vehicles for dissemination in mice.
abstract: Peripheral blood myelomonocytic cells are important for cytomegalovirus dissemination to distal organs such as salivary glands where persistent replication and shedding dictates transmission patterns. We find that this process is markedly enhanced by the murine cytomegalovirus (MCMV)-encoded CC chemokine, MCK2, which promotes recruitment of CX3CR1(hi) patrolling monocytes to initial infection sites in the mouse. There, these cells become infected and traffic via the bloodstream to distal sites. In contrast, inflammatory monocytes, the other major myelomonocytic subset, remain virus negative. CX3CR1 deficiency prevents patrolling monocyte migration on the vascular endothelium and interrupts MCMV dissemination to the salivary glands independent of antiviral NK and T cell immune control. In this manner, CX3CR1(hi) patrolling monocytes serve as immune-privileged vehicles to transport MCMV via the bloodstream to distal organs. MCMV commandeers patrolling monocytes to mediate systemic infection and seed a persistent reservoir essential for horizontal transmission.
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Daley-Bauer
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Roback
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Grace M
authors.initials: GM
authors.lastname: Wynn
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: mocarski@emory.edu.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Mocarski
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D019742:Chemokines, CC / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology*; D004195:Disease Models, Animal; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000737:chemistry* / Q000276:immunology / Q000821:virology*; D018146:Muromegalovirus / Q000276:immunology / Q000502:physiology*; D019707:Receptors, Chemokine / Q000032:analysis*; D012469:Salivary Glands / Q000821:virology; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D000073883:CX3C Chemokine Receptor 1; D019742:Chemokines, CC; C471885:Cx3cr1 protein, mouse; C121663:MCK-2 protein, Mouse cytomegalovirus 1; D019707:Receptors, Chemokine; D014764:Viral Proteins