Suling Kristen, Quinn Gary, Wood James, Patience Clive
Immerge BioTherapeutics Inc., 300 Technology Square, Cambridge, MA 02129, USA.
Virology. 2003 Aug 1;312(2):330-6. doi: 10.1016/s0042-6822(03)00380-5.
The chronic shortage of human donor organs and tissues for allotransplantation could be relieved if clinical xenotransplantation were to become a viable clinical therapy. Balanced against the benefits of xenotransplantation are the possible consequences of zoonotic infections, and in particular, infection by porcine endogenous retrovirus (PERV). An often-proclaimed risk of PERV infection is the possible recombination of PERV with human endogenous retroviruses (HERV). To address this issue, we examined the potential for HERV sequences to be cross-packaged into PERV particles produced from infected human 293 cells. Although HERV-K, W, E, R, and ERV-9 RNA transcripts are expressed in 293 cells, we did not detect cross-packaging of any of these HERV groups. Quantitative analysis indicated that less than approximately 1 in 10(4)-10(7) PERV particles might contain HERV sequences. In comparison, we found that murine leukemia virus (MLV)-based vector transcripts were cross-packaged at a rate of approximately one copy in 10(4) PERV particles. Our results indicate that the potential for recombination of PERV and HERV sequences is low and that novel viruses generated by this mechanism are unlikely to represent a significant risk for xenotransplantation.
如果临床异种移植能成为一种可行的临床治疗方法，那么同种异体移植中人体供体器官和组织长期短缺的问题有望得到缓解。与异种移植的益处相权衡的是动物源性感染的可能后果，尤其是猪内源性逆转录病毒（PERV）感染。人们常宣称的PERV感染风险是PERV与人内源性逆转录病毒（HERV）可能发生重组。为解决这一问题，我们研究了HERV序列被包装进由受感染的人293细胞产生的PERV颗粒中的可能性。尽管HERV-K、W、E、R和ERV-9 RNA转录本在293细胞中表达，但我们未检测到这些HERV组中的任何一组发生交叉包装。定量分析表明，每10⁴ - 10⁷个PERV颗粒中可能不到1个含有HERV序列。相比之下，我们发现基于鼠白血病病毒（MLV）的载体转录本以每10⁴个PERV颗粒约1个拷贝的速率被交叉包装。我们的结果表明，PERV与HERV序列发生重组的可能性较低，且由此机制产生的新型病毒不太可能对异种移植构成重大风险。
