EXPRESSION & FUNCTION OF A CMV CHEMOKINE IN PATHOGENESIS

描述：这项研究提出调查的表达和 小鼠巨细胞病毒趋化因子同源物的功能作用 （MCMV）。 麦克唐纳博士指出，MCMV开放的推导序列 阅读框与CC（Beta）类的成员高度同源， 趋化因子 这是第一个病毒可能产生 细胞因子及其受体。 β趋化因子是哺乳动物的小分子 其对白细胞（包括单核细胞/巨噬细胞）、细胞 在CMV感染中起着重要作用。 利用体外趋化性， 钙动员和结合试验，麦克唐纳博士将确定 这种称为MCK-1的趋化因子同系物是否表现出激动剂或 对存在于原发灶上的内源性趋化因子受体的拮抗剂活性 鼠巨噬细胞以及巨噬细胞系。 RNA的表达 编码MCK-1的基因将在感染组织中通过分子方法进行表征 培养细胞以及感染小鼠的组织中。 MCK-1的作用 在MCMV中，将通过给予MCK-1来研究发病机理 中和抗体，并通过产生重组MCMV缺乏 功能性MCK-1 对组织病毒滴度、LD 50和炎症的影响 答案将被确定。 这些研究将提供深入了解 趋化因子在HCMV发病机制中的作用，导致可能的治疗 和/或对这种人类病原体的预防性干预。

DESCRIPTION: The research proposed investigates the expression and functional role of a chemokine homologue encoded by murine cytomegalovirus (MCMV). Dr. MacDonald has noted that the deduced sequence of a MCMV open reading frame is highly homologous to members of the CC (Beta) class of chemokines. This is the first example of a virus possibly producing a cytokine and its receptor. Beta chemokines are small mammalian molecules which are chemotactic for leukocytes, including monocyte/macrophages, cells that play a prominent role in CMV infection. Utilizing in vitro chemotaxis, calcium mobilization and binding assays, Dr. MacDonald will determine whether this chemokine homologue, designated MCK-1, exhibits agonist or antagonist activity for endogenous chemokine receptors present on primary murine macrophages, as well as macrophage cell lines. The expression of RNA encoding MCK-1 will be characterized by molecular methods in infected tissue culture cells, as well as in tissues from infected mice. The role of MCK-1 in MCMV pathogenesis will be investigated by administration of MCK-1 neutralizing antibodies and by the generation of a recombinant MCMV lacking functional MCK-1. Effects on tissue viral titers, LD50 and the inflammatory response will be determined. These studies will provide insight into the role of chemokines in HCMV pathogenesis, leading to possible therapeutic and/or preventative interventions for this human pathogen.