Miller-Kittrell Mindy, Sai Jiqing, Penfold Mark, Richmond Ann, Sparer Tim E
Department of Microbiology, University of Tennessee, Walters Life Sciences Rm F417, Knoxville, TN 37996, USA.
Virology. 2007 Aug 1;364(2):454-65. doi: 10.1016/j.virol.2007.03.002. Epub 2007 Apr 11.
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.
人巨细胞病毒(HCMVs)是免疫功能低下患者和新生儿的重要病原体。HCMV托莱多(Tol)株的病毒趋化因子vCXCL-1与HCMV毒力有关。黑猩猩巨细胞病毒(CCMV)有几个与vCXCL-1(Tol)基因UL146相似的基因。为了测试CCMV病毒趋化因子vCXCL-1(CCMV)是否与vCXCL-1(Tol)相似,我们在体外对其功能进行了表征。比较了vCXCL-1(Tol)、vCXCL-1(CCMV)与宿主趋化因子在中性粒细胞中的受体结合、激活、趋化性、信号传导和凋亡情况。尽管同源物具有相似的激活潜能、趋化特性和信号传导,但vCXCL-1(CCMV)对CXCR2的亲和力低约70倍,并且在整合素上调和中性粒细胞凋亡方面存在差异。这些数据表明,尽管vCXCL-1存在广泛的氨基酸变异性,但CCMV可能为评估vCXCL-1在体内CMV发病机制中的作用提供一个模型。