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小鼠巨细胞病毒sgg1基因的结构与功能:唾液腺腺泡细胞中病毒生长的一个决定因素。

Structure and function of the murine cytomegalovirus sgg1 gene: a determinant of viral growth in salivary gland acinar cells.

作者信息

Lagenaur L A, Manning W C, Vieira J, Martens C L, Mocarski E S

机构信息

Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305-5402.

出版信息

J Virol. 1994 Dec;68(12):7717-27. doi: 10.1128/JVI.68.12.7717-7727.1994.

DOI:10.1128/JVI.68.12.7717-7727.1994
PMID:7966561
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC237233/
Abstract

The salivary gland has long been recognized as an important target organ for cytomegalovirus replication in the infected host. A viral gene, denoted sgg1, plays an important role for replication in the salivary gland even though it is dispensable for growth in other organs or in cultured cells. The nucleotide sequence of this gene and of cDNA clones representing two spliced transcripts (1.5 and 1.8 kb in size) has been determined. The more abundant 1.5-kb transcript contains a 312-amino-acid (aa) open reading frame (ORF) and encodes the corresponding 37-kDa protein (Sgg1) when expressed in transfected COS-7 cells. The 1.8-kb transcript initiates upstream of the 1.5-kb transcript and contains a 108-aa ORF in addition to the 312-aa ORF. This longer cDNA also encodes the 37-kDa protein Sgg1, although at lower abundance than the 1.5-kb cDNA. Sgg1 localizes to the cytoplasm of COS-7 cells, which is consistent with the predicted structural characteristics of the 312-aa ORF: a type 1 integral membrane protein. During viral infection, expression of both sgg1 transcripts is highest at early times (8 to 12 h) after infection; only the 1.5-kb transcript is present, at low levels, late in infection. A recombinant virus, RM868, carrying a lacZ-gpt insertion within sgg1, fails to express Sgg1 protein and exhibits reduced growth in the salivary gland. RM868 retains the capacity to disseminate in the infected mouse and to enter serous acinar cells, although it fails to replicate efficiently in this cell type. These results suggest that sgg1 is critical for high levels of viral replication in the salivary gland.

摘要

唾液腺长期以来一直被认为是巨细胞病毒在受感染宿主体内复制的重要靶器官。一种名为sgg1的病毒基因,尽管它对于在其他器官或培养细胞中的生长并非必需,但在唾液腺的复制中起着重要作用。已经确定了该基因以及代表两种剪接转录本(大小分别为1.5和1.8 kb)的cDNA克隆的核苷酸序列。含量更丰富的1.5 kb转录本包含一个312个氨基酸(aa)的开放阅读框(ORF),当在转染的COS - 7细胞中表达时,编码相应的37 kDa蛋白(Sgg1)。1.8 kb转录本在1.5 kb转录本的上游起始,除了312个氨基酸的ORF外,还包含一个108个氨基酸的ORF。这个更长的cDNA也编码37 kDa蛋白Sgg1,尽管其丰度低于1.5 kb的cDNA。Sgg1定位于COS - 7细胞的细胞质中,这与312个氨基酸的ORF的预测结构特征一致:一种1型整合膜蛋白。在病毒感染期间,两种sgg1转录本的表达在感染后的早期(8至12小时)最高;在感染后期,仅存在低水平的1.5 kb转录本。一种在sgg1内携带lacZ - gpt插入的重组病毒RM868,无法表达Sgg1蛋白,并且在唾液腺中的生长受到抑制。RM868保留了在受感染小鼠中传播并进入浆液性腺泡细胞的能力,尽管它在这种细胞类型中无法有效复制。这些结果表明,sgg1对于唾液腺中高水平的病毒复制至关重要。

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