中国特有小型猪中pol基因缺陷型猪内源性反转录病毒的系统鉴定及可能引发的病理效应研究

中国特有小型猪有望发展为异种移植的优良供体。猪内源性反转录病毒（PERV）是猪→人异种移植、猪源生物活性材料中最受关注的病原体。由于PERV存在跨种传播可能性，国内外学者尝试多种方法以消除PERV传染风险。我们在前期研究中选育了无PERV传染性五指山小型猪（WZSP）并初步鉴定出PERV-pol基因缺陷型WZSP。基于前期研究基础，我们拟对WZSP中pol基因缺陷型PERV进行系统鉴定和研究。首先通过全基因组重测序、转录组测序、构建PERV-pol基因截短体并进行功能验证，从而确认pol基因缺陷型PERV；其次对小型猪中pol基因缺陷型PERV的遗传稳定性进行研究；最后对PERV-pol基因缺陷可能引发的病理效应进行探索。本研究将为选育PERV-pol基因缺陷型WZSP新品系奠定基础，对于我国特有小型猪资源的开发利用具有重要意义，也有助于异种移植病毒安全性的深入评价。

Chinese miniature pigs are expected to be suitable xenotransplantation donor animals. Porcine endogenous retrovirus (PERV) is the most concerned pathogen in xenotransplantation and porcine biopharmaceuticals. Due to the possibility of cross-species transmission of PERV, scientists have tried various methods to eliminate the risk of PERV infection. In previous studies, we selected Wuzhishan pigs (WZSP) that did not transmit PERV to human cells, i.e., non-transmitting pigs, and we preliminarily identified WZSP with defective PERV pol genes. Based on results of the previous studies, we plan to systematically identify and study PERV with defective pol genes in WZSP. In this study, firstly, several experiments including whole-genome resequencing, transcriptome sequencing, construction and characterization of truncated PERV pol genes will be conducted in order to confirm PERV with defective pol genes. Secondly, the genetic stability of PERV with defective pol genes in miniature pigs will be studied. Finally, the possible pathological effects caused by PERV pol gene defects will be explored. This study will set foundation for breeding a novel WZSP strain with defective PERV pol genes. Moreover, this study is important for the development and utilization of the Chinese miniature pigs, and it will contribute to the further appraisal of the viral safety of xenotransplantation.