Mavinakere Manohara S, Colberg-Poley Anamaris M
Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA.
Department of Pediatrics, George Washington University, School of Medicine and Health Sciences, 111 Michigan Avenue NW, Washington, DC 20010, USA.
J Gen Virol. 2004 Feb;85(Pt 2):323-329. doi: 10.1099/vir.0.19589-0.
The human cytomegalovirus (HCMV) UL37 immediate-early (IE) gene minimally encodes three protein isoforms that share NH(2)-terminal sequences. The predominant UL37 isoform detected during HCMV infection was the UL37 exon 1 protein (pUL37x1), which was produced from IE and, more abundantly, through late times of infection. pUL37x1 was localized in both the endoplasmic reticulum (ER) and mitochondria in infected cells. To determine which UL37x1 NH(2)-terminal residues serve as ER and mitochondrial targeting signals, we examined the subcellular localization of two deletion mutants. pUL37x1Delta2-23, which lacks the hydrophobic leader, is neither translocated into the ER nor imported mitochondrially; conversely, pUL37x1Delta23-34, lacking the juxtaposed basic residues, was translocated into the ER but only imported weakly into mitochondria. These studies show for the first time the temporal production and localization of pUL37x1 during HCMV infection. The trafficking patterns of mutants suggest that the pUL37x1 targeting signal to ER and mitochondria is bipartite.
人巨细胞病毒（HCMV）UL37立即早期（IE）基因最少编码三种具有共同氨基末端序列的蛋白质异构体。在HCMV感染期间检测到的主要UL37异构体是UL37外显子1蛋白（pUL37x1），它由IE产生，并且在感染后期产生得更为丰富。pUL37x1定位于受感染细胞的内质网（ER）和线粒体中。为了确定哪些UL37x1氨基末端残基作为ER和线粒体靶向信号，我们检测了两个缺失突变体的亚细胞定位。缺少疏水前导序列的pUL37x1Delta2 - 23既不转运到ER中也不导入线粒体；相反，缺少相邻碱性残基的pUL37x1Delta23 - 34转运到ER中，但仅微弱地导入线粒体。这些研究首次展示了pUL37x1在HCMV感染期间的产生时间和定位。突变体的运输模式表明，pUL37x1靶向ER和线粒体的信号是双组分的。
