CHARACTERIZATION OF HCMV UL84

HCMV UL84 的表征

• 批准号: 6341734
• 负责人: GREGORY S PARI
• 金额: $ 27.12万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-15 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6341734
• 关键词: DNA replication; cytomegalovirus; gene expression; genetic mapping; genetic regulation; genetic transcription; messenger RNA; protein structure function; virus genetics; virus infection mechanism; virus protein

Human cytomegalovirus (HCMV) is a ubiquitous herpes virus causing mild or subclinical disease in immunocompetent adults. However, severe complications may be encountered in immunocompromised individuals. HCMV is a systemic infection that may infect several sites in the body, including the retina, gastrointestinal tract, lungs, liver and central nervous system. Initially it is was shown that human cytomegalovirus (HCMV) required eleven distinct loci for origin-dependent DNA replication. In later studies it was demonstrated that, of the eleven loci originally described, UL84 appeared to be the only non- core replication protein required for oriLyt-dependent replication. This fact, coupled with the observation that RNA-DNA hybrid structures are present within HCMV oriLyt, suggests the possibility that HCMV may have a mode of initiation of DNA replication unlike that of other herpesviruses. UL84 may be the key factor involved in initiation of HCMV DNA replication and, therefore, an ideal target for chemotherapeutic agents needed to control infection. To this end, this proposal will define the role of UL84 in the initiation of HCMV DNA replication and effects on cellular processes. The UL84 protein is required for HCMV DNA replication as demonstrated in transient assays and with a viral mutant. The elucidation of a function for UL84 will allow for the development of anti-HCMV drugs. Our hypothesis is that UL84 is involved in the initiation of HCMV DNA replication by a direct interaction with the origin of replication, oriLyt, and participates in the regulation of host cell RNA processing.

人类巨细胞病毒（HCMV）是一种普遍存在的疱疹病毒，在免疫能力的成年人中引起轻度或亚临床疾病。 但是，免疫功能低下的个体可能会遇到严重的并发症。 HCMV是一种全身感染，可能感染体内几个部位，包括视网膜，胃肠道，肺，肝脏和中枢神经系统。最初，人们表明，人类巨细胞病毒（HCMV）需要11个不同的基因座才能依赖于起源的DNA复制。 在后来的研究中，有证据表明，在最初描述的11个基因座中，UL84似乎是依赖Orilyt依赖性复制所需的唯一非核心复制蛋白。 这一事实以及观察到HCMV Orilyt中存在RNA-DNA杂交结构的观察结果表明，HCMV可能具有与其他疱疹病毒不同的DNA复制方式的可能性。 UL84可能是启动HCMV DNA复制的关键因素，因此是控制感染所需的化学治疗剂的理想靶标。 为此，该建议将定义UL84在HCMV DNA复制启动中的作用以及对细胞过程的影响。 如瞬态测定和病毒突变体中所示的HCMV DNA复制所必需的UL84蛋白。 UL84功能的阐明将允许抗HCMV药物的发展。 我们的假设是，UL84通过与复制，Orilyt的起源直接相互作用并参与宿主细胞RNA处理的调节，参与了HCMV DNA复制的启动。