Mason A L, Zhang G
Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada.
Gastroenterol Clin Biol. 2010 Aug-Sep;34(6-7):359-66. doi: 10.1016/j.gcb.2010.04.014. Epub 2010 Jun 30.
Several environmental agents have been linked with primary biliary cirrhosis (PBC) that include bacteria, xenobiotics and viruses. A human beta retrovirus (HBRV) related to mouse mammary tumor virus has been cloned and characterized from patients with PBC. This agent can be detected in the majority of patients' perihepatic lymph nodes by immunochemistry and RT-PCR. The HBRV has recently been isolated in culture and integration sites have been identified in the genome of patients to provide convincing evidence of beta retrovirus infection in patients. Three lines of evidence support a role for the virus in PBC. First, the beta retrovirus is linked with aberrant expression of mitochondrial protein(s) on the biliary epithelium cell (BEC) surface, a disease specific phenotype. Second, the related agent, mouse mammary tumor virus has been linked with autoimmune biliary disease in the NOD.c3c4 mouse model for PBC. In this mouse model, the virus is localized to diseased biliary epithelium that also display aberrant expression of the mitochondrial autoantigens. In translational studies, both patients with PBC and NOD.c3c4 mice demonstrate significant improvement in biliary disease with combination antiviral therapy. An overview of the biological relevance of the beta retrovirus infection in PBC will be discussed in this review.
几种环境因素已被认为与原发性胆汁性肝硬化（PBC）有关，其中包括细菌、外源性物质和病毒。一种与小鼠乳腺肿瘤病毒相关的人类β逆转录病毒（HBRV）已从PBC患者中克隆并鉴定出来。通过免疫化学和逆转录聚合酶链反应（RT-PCR）可在大多数患者的肝周淋巴结中检测到这种病原体。最近，HBRV已在培养物中分离出来，并且已在患者基因组中确定了整合位点，从而为患者体内的β逆转录病毒感染提供了令人信服的证据。有三条证据支持该病毒在PBC中起作用。第一，β逆转录病毒与胆管上皮细胞（BEC）表面线粒体蛋白的异常表达有关，这是一种疾病特异性表型。第二，相关病原体小鼠乳腺肿瘤病毒已与PBC的NOD.c3c4小鼠模型中的自身免疫性胆管疾病有关。在这个小鼠模型中，病毒定位于患病的胆管上皮，这些上皮也显示出线粒体自身抗原的异常表达。在转化研究中，PBC患者和NOD.c3c4小鼠在联合抗病毒治疗后胆管疾病均有显著改善。本综述将讨论β逆转录病毒感染在PBC中的生物学相关性概述。
