The role of cytomegalovirus gH/gL glycoprotein complexes in infection

人巨细胞病毒(HCMV)感染是免疫缺陷宿主发病和死亡的主要原因。尽管存在抗巨细胞病毒的治疗方法，但耐药性的快速发展需要新的、补充的策略。例如，抗病毒治疗的常见靶点是促进病毒进入的包膜糖蛋白。疱疹病毒Gh/Gl糖蛋白复合体是病毒侵入过程中病毒被膜与细胞膜融合所必需的。核心的Gh/Gl二聚体被额外的蛋白质补充，这些蛋白质可以与特定的受体结合和/或可能引导病毒颗粒通过特定的退出途径。对于HCMV，已鉴定出两种可供选择的Gh/gl复合体，它们在体外定义了趋向性并影响病毒的释放，但其在人类感染中的作用尚不清楚。本项目的目的是确定巨细胞病毒Gh/gl复合体的细胞受体，并鉴定小鼠巨细胞病毒(MCMV)的同源Gh/gl复合体。然后，将利用MCMV Gh/Gl复合体的缺失突变体在小鼠模型中研究这些复合体的作用。

Human cytomegalovirus (HCMV) infections are a major cause of morbidity and mortality in immunocompromised hosts. Though anti-HCMV therapies exist, the rapid development of resistance calls for new, complementing strategies. Common targets for antiviral therapy are for example envelope glycoproteins which promote virus entry. Herpesvirus gH/gL glycoprotein complexes are essential for fusion of the viral envelope with a cellular membrane in the process of virus entry. The core gH/gL dimer is complemented with additional proteins which can bind to specific receptors and/or may guide the virus particles through specific exit pathways. For HCMV, two alternative gH/gL complexes have been identified, which in vitro define tropism and influence virus release, yet, whose function in the human infection is not clarified. The aims of this project are to identify the cellular receptor through which HCMV gH/gL complexes define tropism for certain cell types and to identify the homologous gH/gL complexes of the murine cytomegalovirus (MCMV). Then the role of these complexes will be studied in vivo in the mouse model using deletion mutants of MCMV gH/gL complexes.