Spector David J
Department of Microbiology and Immunology, College of Medicine, The Pennsylvania State University, H107, 500 University Drive, Hershey, PA 17033, USA.
Virology. 2015 Feb;476:345-354. doi: 10.1016/j.virol.2014.12.031. Epub 2015 Jan 9.
The UL84 gene of human cytomegalovirus (HCMV) is thought to be involved in the initiation of viral DNA replication, and is essential for replication of strains AD169 and Towne. Hence, discovery that strain TB40-BAC4 is viable in the absence of UL84 presented an enigma requiring an explanation. Data reported here show that strain TR also tolerated loss of UL84, whereas strains FIX, Merlin, Ph, and Toledo did not. UL84-independent growth required the viral replication origin. The genetic locus in TB40 that controls UL84 dependence was mapped to codon 388 of the UL122 gene, which encodes the immediate early 2 (IE2) 86kD protein. Introduction of this TB40-BAC4 variant (H388D) into FIX and Toledo clones converted these strains to UL84 independence. These results provide genetic evidence in virus-infected cells that supports the hypothesis that UL122 participates in the initiation of viral DNA replication by a mechanism involving transcription-mediated activation of the origin.
人巨细胞病毒（HCMV）的UL84基因被认为参与病毒DNA复制的起始过程，对于AD169和Towne毒株的复制至关重要。因此，发现TB40 - BAC4毒株在没有UL84的情况下仍能存活，这是一个需要解释的谜。此处报告的数据表明，TR毒株也能耐受UL84的缺失，而FIX、Merlin、Ph和Toledo毒株则不能。不依赖UL84的生长需要病毒复制起点。TB40中控制对UL84依赖性的基因座被定位到UL122基因的第388密码子，该基因编码立即早期2（IE2）86kD蛋白。将这种TB40 - BAC4变体（H388D）引入FIX和Toledo克隆中，可使这些毒株转变为不依赖UL84。这些结果在病毒感染细胞中提供了遗传学证据，支持了UL122通过涉及转录介导的起点激活机制参与病毒DNA复制起始的假说。
