Walleye dermal sarcoma virus Orf C is targeted to the mitochondria.
Walleye dermal sarcoma virus Orf C is targeted to the mitochondria.
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白眼真皮肉瘤病毒 Orf C 的目标是线粒体。
DOI：
10.1099/vir.0.18570-0
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Quackenbush,SandraL
中科院分区：
文献类型：
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作者：
Nudson,WadeA;Rovnak,Joel;Buechner,Matthew;Quackenbush,SandraL
大眼皮肤肉瘤与一种复杂的逆转录病毒，大眼皮肤肉瘤病毒（WDSV）的存在有关。这些肉瘤在自然感染的鱼中季节性地发展和消退。WDSV除gag、polandenv外，还含有3个开放阅读框架（ORF），分别命名为dorf a、orf bandorf c，orf cis位于5′端重复序列和gag之间。发育中的肿瘤含有低水平的转录本，而退化的肿瘤含有高水平的基因组转录本和病毒颗粒。Orf C蛋白由全长基因组转录物编码，并且可以用抗Orf C特异性抗血清在肿瘤提取物中检测到。为了确定WDSV Orf C的亚细胞位置，用编码血凝素标记的Orf C的表达载体转染培养的细胞，并通过免疫荧光进行检查。Orf C在整个细胞质中观察到，并积累在细胞器中。Orf C和线粒体细胞色素双抗体染色显示Orf C与线粒体共定位，线粒体在细胞质中的正常分布丧失。瞬时表达Orf C的细胞表现出凋亡形态和增加的表面磷脂酰丝氨酸水平，并且不能保留MitoTracker橙子，一种在活性线粒体中积累的染料。这些结果意味着WDSV Orf C在线粒体功能改变中的功能作用，导致细胞凋亡，从而促进肿瘤消退。
Walleye dermal sarcomas are associated with the presence of a complex retrovirus, walleye dermal sarcoma virus (WDSV). These sarcomas develop and regress seasonally in naturally infected fish. In addition togag,polandenv, WDSV contains three open reading frames (ORFs), designatedorf a,orf bandorf c.orf cis located between the 5′ long terminal repeat andgag. Developing tumours contain low levels oforf aandorf btranscripts, whereas regressing tumours contain high levels of genomic transcripts and virus particles. Orf C protein is encoded by the full-length, genomic transcript and can be detected in tumour extracts with anti-Orf C-specific antisera. To determine the subcellular location of WDSV Orf C, cultured cells were transfected with an expression vector encoding haemagglutinin-tagged Orf C and examined by immunofluorescence. Orf C was observed throughout the cytoplasm and accumulated in cytoplasmic organelles. Dual-antibody staining for Orf C and mitochondrial cytochromecdemonstrated colocalization of Orf C with mitochondria and loss of the normal distribution of mitochondria in the cytoplasm. Cells transiently expressing Orf C exhibited apoptotic morphology and increased levels of surface phosphatidylserine and were unable to retain MitoTracker Orange, a dye that accumulates in active mitochondria. These results imply a functional role for WDSV Orf C in an alteration of mitochondrial function that results in apoptosis contributing to tumour regression.