The human cytomegalovirus UL76 gene regulates the level of expression of the UL77 gene.
The human cytomegalovirus UL76 gene regulates the level of expression of the UL77 gene.
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DOI：
10.1371/journal.pone.0011901
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发表时间：
2010-07-30
期刊：
影响因子：
3.7
通讯作者：
Tsurumi T
中科院分区：
文献类型：
--
作者：
Isomura H;Stinski MF;Murata T;Nakayama S;Chiba S;Akatsuka Y;Kanda T;Tsurumi T
人巨细胞病毒(HCMV)可在免疫抑制条件下重新激活，导致多种致命性肺炎、肝炎、视网膜炎和胃肠道疾病。当怀孕期间发生原发感染时，巨细胞病毒也会导致新生儿耳聋和智力低下。在HCMV基因组中，已预测到至少194个已知的开放阅读框架(ORF)，其中约四分之一，即41个ORF，是病毒在细胞培养中复制所必需的。相反，大多数预测的开放阅读框对细胞培养中的病毒复制不是必需的。然而，这些开放阅读框也可能是病毒在宿主中有效复制所必需的。巨细胞病毒UL77基因是病毒复制所必需的，并在病毒DNA包装中发挥作用。目前，人巨细胞病毒感染细胞中UL76上游基因的功能尚不清楚。UL76和UL77是同一病毒mRNA上的启动子，未检测到UL77的常规5‘端mRNA。绝大多数真核生物的mRNAs是单顺反子的，即它们只编码一种蛋白质。为了确定UL76ORF是否影响UL77基因的表达，我们通过ORF移码、终止密码子或病毒基因的缺失来突变UL76。通过转染表达载体或感染重组病毒来确定对UL77蛋白表达的影响。UL76ORF突变显著增加了UL77蛋白的表达水平。然而，UL77ORF上游UL76的缺失对病毒生长的影响微乎其微。虽然UL76对病毒复制不是必需的，但UL76 ORF以一种依赖于翻译重新启动的方式参与调节UL77蛋白的表达水平。UL76可以微调UL77的表达，使病毒在HCMV感染的细胞中有效复制。
Human cytomegalovirus (HCMV) can be reactivated under immunosuppressive conditions causing several fatal pneumonitis, hepatitis, retinitis, and gastrointestinal diseases. HCMV also causes deafness and mental retardation in neonates when primary infection has occurred during pregnancy. In the genome of HCMV at least 194 known open reading frames (ORFs) have been predicted, and approximately one-quarter, or 41 ORFs, are required for viral replication in cell culture. In contrast, the majority of the predicted ORFs are nonessential for viral replication in cell culture. However, it is also possible that these ORFs are required for the efficient viral replication in the host. The UL77 gene of HCMV is essential for viral replication and has a role in viral DNA packaging. The function of the upstream UL76 gene in the HCMV-infected cells is not understood. UL76 and UL77 are cistons on the same viral mRNA and a conventional 5′ mRNA for UL77 has not been detected. The vast majority of eukaryotic mRNAs are monocistronic, i.e., they encode only a single protein. To determine whether the UL76 ORF affects UL77 gene expression, we mutated UL76 by ORF frame-shifts, stop codons or deletion of the viral gene. The effect on UL77 protein expression was determined by either transfection of expression plasmids or infection with recombinant viruses. Mutation of UL76 ORF significantly increased the level of UL77 protein expression. However, deletion of UL76 upstream of the UL77 ORF had only marginal effects on viral growth. While UL76 is not essential for viral replication, the UL76 ORF is involved in regulation of the level of UL77 protein expression in a manner dependent on the translation re-initiation. UL76 may fine-tune the UL77 expression for the efficient viral replication in the HCMV- infected cells.
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DOI：
10.1073/pnas.121164898
发表时间：
2001-06-05
影响因子：
11.1
作者：
Ellis, HM;Yu, DG;Court, DL
通讯作者：
Court, DL
影响因子：
5.4
作者：
Isomura, Hiroki;Stinski, Mark F.;Tsurumi, Tatsuya
通讯作者：
Tsurumi, Tatsuya
影响因子：
5.4
作者：
Mitchell, Dora P.;Savaryn, John P.;Terhune, Scott S.
通讯作者：
Terhune, Scott S.
影响因子：
3.7
作者：
BIEGALKE, BJ;GEBALLE, AP
通讯作者：
GEBALLE, AP
影响因子：
5.4
作者：
DEGNIN, CR;SCHLEISS, MR;GEBALLE, AP
通讯作者：
GEBALLE, AP