Wootton Sarah K, Halbert Christine L, Miller A Dusty
Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.
Nature. 2005 Apr 14;434(7035):904-7. doi: 10.1038/nature03492.
Jaagsiekte sheep retrovirus (JSRV) causes a contagious lung cancer in sheep and goats, with significant animal health and economic consequences. The host range of JSRV is in part limited by species-specific differences in the virus entry receptor, hyaluronidase 2 (Hyal2), which is not functional as a receptor in mice but is functional in humans. Sheep are immunotolerant of JSRV because of the expression of closely related endogenous retroviruses, which are not present in humans and most other species, and this may facilitate oncogenesis. Here we show that expression of the JSRV envelope (Env) protein alone in lungs of mice, by using a replication-incompetent adeno-associated virus vector, results in tumours with a bronchiolo-alveolar localization like those seen in sheep. Whereas lethal disease was observed in immunodeficient mice, tumour development was almost entirely blocked in immunocompetent mice. Our results provide a rare example of an oncogenic viral structural protein, show that interaction of the viral Env protein with the virus entry receptor Hyal2 is not required for tumorigenesis, and indicate that immune recognition of Env can protect against JSRV tumorigenesis.
绵羊肺腺瘤逆转录病毒（JSRV）可引发绵羊和山羊的一种传染性肺癌，造成重大的动物健康问题和经济后果。JSRV的宿主范围部分受限于病毒进入受体透明质酸酶2（Hyal2）的物种特异性差异，该受体在小鼠中无功能，但在人类中有功能。绵羊对JSRV具有免疫耐受性，因为存在密切相关的内源性逆转录病毒，而人类和大多数其他物种中不存在这种病毒，这可能有助于肿瘤发生。在此我们表明，通过使用无复制能力的腺相关病毒载体，仅在小鼠肺中表达JSRV包膜（Env）蛋白，会导致出现具有细支气管肺泡定位的肿瘤，类似于在绵羊中所见的肿瘤。在免疫缺陷小鼠中观察到致死性疾病，而在免疫 competent 小鼠中肿瘤发展几乎完全受阻。我们的结果提供了一个致癌病毒结构蛋白的罕见例子，表明病毒Env蛋白与病毒进入受体Hyal2的相互作用对于肿瘤发生并非必需，并表明对Env的免疫识别可预防JSRV肿瘤发生。 （注：“immunocompetent”原文有误，正确拼写为“immunocompetent”，意为“有免疫活性的”“免疫功能正常的” ）
