Functional characterization of chimpanzee cytomegalovirus chemokine, vCXCL-1(CCMV)

Abstract

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.