Cytomegalovirus MCK-2 controls mobilization and recruitment of myeloid progenitor cells to facilitate dissemination.
Murine cytomegalovirus encodes a secreted, pro-inflammatory chemokine-like protein, MCK-2, that recruits leukocytes and facilitates viral dissemination. We have shown that MCK-2-enhanced recruitment of myelomonocytic leukocytes with an immature phenotype occurs early during infection and is associated with efficient viral dissemination. Expression of MCK-2 drives the mobilization of a population of leukocytes from bone marrow that express myeloid marker Mac-1 (CD11b), intermediate levels of Gr-1 (Ly6 G/C), platelet-endothelial-cell adhesion molecule-1 (PECAM-1, CD31), together with heterogeneous levels of stem-cell antigen-1 (Sca-1, Ly-6 A /E). Recombinant MCK-2 mediates recruitment of this population even in the absence of viral infection. Recruitment of this cell population and viral dissemination via the bloodstream to salivary glands proceeds normally in mice that lack CCR2 and MCP-1 (CCL2), suggesting that recruitment of macrophages is not a requisite component of pathogenesis. Thus, a systemic impact of MCK-2 enhances the normal host response and causes a marked increase in myelomonocytic recruitment with an immature phenotype to initial sites of infection. Mobilization influences levels of virus dissemination via the bloodstream to salivary glands and is dependent on a myelomonocytic cell type other than mature macrophages.
Noda
Satoshi
S
Department of Microbiology and Immunology, Stanford University School of Medicine, Fairchild Science Bldg, 299 Campus Dr, Stanford, CA 94305-5124, USA.
Aguirre
Shirley A
SA
Bitmansour
Andrew
A
Brown
Janice M
JM
Sparer
Timothy E
TE
Huang
Jing
J
Mocarski
Edward S
ES
D016475:3T3 Cells; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001853:Bone Marrow / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D019742:Chemokines, CC / Q000494:pharmacology*; D016130:Immunophenotyping; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology; D051379:Mice; D018146:Muromegalovirus / Q000472:pathogenicity*; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology; D011994:Recombinant Proteins; D014764:Viral Proteins / Q000494:pharmacology*
D015415:Biomarkers; D019742:Chemokines, CC; C121663:MCK-2 protein, Mouse cytomegalovirus 1; D011994:Recombinant Proteins; D014764:Viral Proteins