title: A little cooperation helps murine cytomegalovirus (MCMV) go a long way: MCMV co-infection rescues a chemokine salivary gland defect.
abstract: Cytomegaloviruses (CMVs) produce chemokines (vCXCLs) that have both sequence and functional homology to host chemokines. Assessment of vCXCL-1's role in CMV infection is limited to in vitro and in silico analysis due to CMVs species specificity. In this study, we used the murine CMV (MCMV) mouse model to evaluate the function of vCXCL-1 in vivo. Recombinant MCMVs expressing chimpanzee CMV vCXCL-1 (vCXCL-1CCMV) or host chemokine, mCXCL1, underwent primary dissemination to the popliteal lymph node, spleen and lung similar to the parental MCMV. However, neither of the recombinants expressing chemokines was recovered from the salivary gland (SG) at any time post-infection although viral DNA was detected. This implies that the virus does not grow in the SG or the overexpressed chemokine induces an immune response that leads to suppressed growth. Pointing to immune suppression of virus replication, recombinant viruses were isolated from the SG following infection of immune-ablated mice [i.e. SCID (severe combined immunodeficiency), NSG (non-obese diabetic SCID gamma) or cyclophosphamide treated]. Depletion of neutrophils or NK cells does not rescue the recovery of chemokine-expressing recombinants in the SG. Surprisingly we found that co-infection of parental virus and chemokine-expressing virus leads to the recovery of the recombinants in the SG. We suggest that parental virus reduces the levels of chemokine expression leading to a decrease in inflammatory monocytes and subsequent SG growth. Therefore, aberrant expression of the chemokines induces cells of the innate and adaptive immune system that curtail the growth and dissemination of the recombinants in the SG.
authors.affiliation: Department of Microbiology, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN 37996, USA.
authors.forename: Pranay
authors.initials: P
authors.lastname: Dogra
authors.affiliation: Department of Microbiology, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN 37996, USA.
authors.forename: Mindy
authors.initials: M
authors.lastname: Miller-Kittrell
authors.affiliation: Department of Microbiology, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN 37996, USA.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pitt
authors.affiliation: Department of Microbiology, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN 37996, USA.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Jackson
authors.affiliation: Department of Microbiology, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN 37996, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Masi
authors.affiliation: Department of Microbiology, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN 37996, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Copeland
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0524, USA.
authors.forename: Shuen
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0524, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Miller
authors.affiliation: Department of Microbiology, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN 37996, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparer
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D051379:Mice; D016513:Mice, SCID; D018146:Muromegalovirus / Q000235:genetics / Q000276:immunology*; D002679:Pan troglodytes; D012469:Salivary Glands / Q000276:immunology / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D019743:Chemokines, CXC; D014764:Viral Proteins; C121017:viral chemokine CXC-1, Cytomegalovirus