Isomura Hiroki, Stinski Mark F, Kudoh Ayumi, Nakayama Sanae, Iwahori Satoko, Sato Yoshitaka, Tsurumi Tatsuya
Division of Virology, Aichi Cancer Center Research Institute, 1-1, Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
J Virol. 2007 Jun;81(12):6197-206. doi: 10.1128/JVI.00089-07. Epub 2007 Apr 4.
Transcription of the DNA polymerase processivity factor gene (UL44) of human cytomegalovirus initiates at three distinct start sites, which are differentially regulated during productive infection. Two of these start sites, the distal and proximal sites, are active at early times, and the middle start site is active at only late times after infection (F. Leach and E. S. Mocarski, J. Virol. 63:1783-1791, 1989). Compared to the wild type, UL44 gene expression was lower for recombinant viruses with the distal or the middle TATA element mutated. The transcripts initiating from the distal or middle start site facilitated late viral gene expression. The level of viral DNA synthesis was affected by mutation of the distal TATA element. In contrast, mutation of the middle TATA element did not affect the level of viral DNA synthesis, but it did affect significantly the level of late viral gene expression. Recombinant viruses with the distal or middle TATA element mutated grew more slowly than the wild type at both low and high multiplicities of infection. Reduced expression of the UL44 gene from the late middle viral promoter correlated with decreased late viral protein expression and decreased viral growth.
人巨细胞病毒的DNA聚合酶持续合成因子基因(UL44)的转录起始于三个不同的起始位点,在增殖性感染期间受到不同的调控。其中两个起始位点,即远端和近端位点,在早期是活跃的,而中间起始位点仅在感染后的晚期才活跃(F. 利奇和E. S. 莫卡尔斯基,《病毒学杂志》63:1783 - 1791, 1989)。与野生型相比,远端或中间TATA元件发生突变的重组病毒的UL44基因表达较低。从远端或中间起始位点起始的转录本促进了病毒晚期基因的表达。病毒DNA合成水平受远端TATA元件突变的影响。相比之下,中间TATA元件的突变不影响病毒DNA合成水平,但确实显著影响病毒晚期基因的表达水平。远端或中间TATA元件发生突变的重组病毒在低感染复数和高感染复数时生长都比野生型慢。来自病毒晚期中间启动子的UL44基因表达降低与病毒晚期蛋白表达减少和病毒生长减缓相关。