Functional characterization of chimpanzee cytomegalovirus chemokine, vCXCL-1(CCMV).
Human cytomegaloviruses (HCMVs) are important pathogens in immunocompromised patients and newborns. The viral chemokine, vCXCL-1, of the Toledo (Tol) strain of HCMV has been implicated in HCMV virulence. Chimpanzee CMV (CCMV) has several genes with similarity to the vCXCL-1(Tol) gene, UL146. In order to test whether the CCMV viral chemokine, vCXCL-1(CCMV), is similar to vCXCL-1(Tol), we characterized its function in vitro. Receptor binding, activation, chemotaxis, signaling, and apoptosis in neutrophils were compared between vCXCL-1(Tol) and vCXCL-1(CCMV) and host chemokines. Although the homologues had similar activation potentials, chemotactic properties, and signaling, vCXCL-1(CCMV) had a approximately 70-fold lower affinity for CXCR2 and displayed differences in integrin upregulation and neutrophil apoptosis. These data demonstrate that in spite of extensive amino acid variability in vCXCL-1, CCMV may provide a model for assessing the role of vCXCL-1 in CMV pathogenesis in vivo.
Miller-Kittrell
Mindy
M
Department of Microbiology, University of Tennessee, Walters Life Sciences Rm F417, Knoxville, TN 37996, USA.
Sai
Jiqing
J
Penfold
Mark
M
Richmond
Ann
A
Sparer
Tim E
TE
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D016367:Baculoviridae / Q000235:genetics; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D020013:Calcium Signaling; D019743:Chemokines, CXC / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D017124:Conserved Sequence; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology / Q000473:pathology / Q000821:virology; D002679:Pan troglodytes / Q000276:immunology / Q000821:virology*; D021382:Protein Sorting Signals / Q000235:genetics; D023063:Receptors, Interleukin-8B / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D014774:Virulence / Q000235:genetics / Q000276:immunology
D039481:CD11b Antigen; D039521:CD11c Antigen; D019743:Chemokines, CXC; C509295:ITGAM protein, human; D021382:Protein Sorting Signals; D023063:Receptors, Interleukin-8B; D014764:Viral Proteins