Retroviral aetiopathogenesis of ovinepulmonary carcinoma: A critical appraisal

S.J. Hecht , J.M. Sharp , J.C. Demartini
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引用次数: 24

Abstract

Although it has long been thought that a retrovirus is the responsible agent for ovine pulmonary carcinoma (OPC), identification of a replicative viral agent has proven difficult. Recently, the genome of a new retrovirus, jaagsiekte sheep retrovirus (JSRV), found in the lung-was of affected sheep lung, has bee cloned and sequenced; characterization of this virus and its consistent presence in tumor cells argue for its role as the aetiologic agent of OPC. Analysis of the nucleic acid sequence of the JRSV genome, suggests a new class of retrovirus, one that is chimeric according to the morphological classification scheme used for retroviruses. The genome of this virus does not appear to contain an oncogene, and the mechanism by which it causes disease is still unknown. The presence of multiple copies of endogenous retroviruses related to JSRV in DNA of OPC-affected and unaffected sheep further complicates investigation of oncogenesis in OPC. This review examines the evidence for a retrovirus as the causative agent for OPC, with particular emphasis on the viruses studied to date. The significance of endogenous, JSRV-related sequences is considered. The mechanisms by which a retrovirus such as JSRV might induce lung tumours in sheep, and which of these are most likely, are discussed in light of these developments, as are the prospects for new means of diagnosis and treatment of this disease.

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肺癌逆转录病毒的发病机制:一个关键的评估
尽管长期以来人们一直认为逆转录病毒是绵羊肺癌(OPC)的致病因子,但事实证明,鉴定复制性病毒因子是很困难的。最近,一种新的逆转录病毒——羊jaagsiekte逆转录病毒(JSRV)的基因组被克隆并测序,该病毒是在受感染羊的肺中发现的;这种病毒的特征及其在肿瘤细胞中的持续存在证明了它作为OPC的病原因子的作用。对JRSV基因组的核酸序列分析表明,这是一种新的逆转录病毒,根据逆转录病毒的形态分类方案,它是嵌合的。这种病毒的基因组似乎不含致癌基因,其致病机制仍不清楚。在OPC感染和未感染绵羊的DNA中存在与JSRV相关的内源性逆转录病毒的多个拷贝,进一步使OPC肿瘤发生的研究复杂化。本综述审查了逆转录病毒作为OPC病原体的证据,特别强调了迄今为止研究的病毒。考虑了内源性jsrv相关序列的重要性。根据这些进展,讨论了诸如JSRV之类的逆转录病毒可能在绵羊中诱发肺部肿瘤的机制,以及其中最可能的机制,以及诊断和治疗这种疾病的新手段的前景。
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