Martina Y, Marcucci K T, Cherqui S, Szabo A, Drysdale T, Srinivisan U, Wilson C A, Patience C, Salomon D R
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
J Virol. 2006 Apr;80(7):3135-46. doi: 10.1128/JVI.80.7.3135-3146.2006.
Porcine endogenous retrovirus (PERV) is considered one of the major risks in xenotransplantation. No valid animal model has been established to evaluate the risks associated with PERV transmission to human patients by pig tissue xenotransplantation or to study the potential pathogenesis associated with PERV infection. In previous work we isolated two genes encoding functional human PERV receptors and proved that introduction of these into mouse fibroblasts allowed the normally nonpermissive mouse cells to become productively infected (T. A. Ericsson, Y. Takeuchi, C. Templin, G. Quinn, S. F. Farhadian, J. C. Wood, B. A. Oldmixon, K. M. Suling, J. K. Ishii, Y. Kitagawa, T. Miyazawa, D. R. Salomon, R. A. Weiss, and C. Patience, Proc. Natl. Acad. Sci. USA 100:6759-6764, 2003). In the present study we created mice transgenic for human PERV-A receptor 2 (HuPAR-2). After inoculation of transgenic animals with infectious PERV supernatants, viral DNA and RNA were detected at multiple time points, indicating productive replication. This establishes the role of HuPAR-2 in PERV infection in vivo; in addition, these transgenic mice represent a new model for determining the risk of PERV transmission and potential pathogenesis. These mice also create a unique opportunity to study the immune response to PERV infection and test potential therapeutic or preventative modalities.
猪内源性逆转录病毒（PERV）被认为是异种移植中的主要风险之一。目前尚未建立有效的动物模型来评估猪组织异种移植将PERV传播给人类患者所带来的风险，也无法研究与PERV感染相关的潜在发病机制。在之前的工作中，我们分离出了两个编码功能性人类PERV受体的基因，并证明将它们导入小鼠成纤维细胞后，通常不具有感染性的小鼠细胞能够被有效感染（T. A. 埃里克森、竹内洋、C. 坦普林、G. 奎因、S. F. 法哈迪安、J. C. 伍德、B. A. 奥德米克森、K. M. 苏林、J. K. 石井、北川洋、宫泽哲、D. R. 所罗门、R. A. 韦斯和C. 佩兴斯，《美国国家科学院院刊》100:6759 - 6764，2003年）。在本研究中，我们培育了转人类PERV - A受体2（HuPAR - 2）基因的小鼠。用感染性PERV上清液接种转基因动物后，在多个时间点检测到病毒DNA和RNA，表明病毒进行了有效复制。这确定了HuPAR - 2在体内PERV感染中的作用；此外，这些转基因小鼠代表了一种新的模型，可用于确定PERV传播的风险和潜在发病机制。这些小鼠还为研究对PERV感染的免疫反应以及测试潜在的治疗或预防方法提供了独特的机会。
