异种移植中猪内源性逆转录病毒的传播

余一凡; 宋佳华; 宋相钦; 李涛; 江建; 白云昊; 王毅

doi:10.3969/j.issn.1674-7445.2023293

异种移植中猪内源性逆转录病毒的传播

doi: 10.3969/j.issn.1674-7445.2023293

余一凡^1,,
宋佳华²,
宋相钦¹,
李涛¹,
江建¹,
白云昊¹,
王毅^1, ,

1.
570216　海口，海南医学院第二附属医院移植研究所
2.
南华大学附属第二医院泌尿外科

基金项目: 国家自然科学基金（82260154）；海南省卫生计生行业科研项目（20A200360）；海南省科技厅自然科学基金（820RC766）；海南医学院2021年度研究生创新科研课题（HYYS2021B0）

详细信息

作者简介:

通讯作者:
王毅（ORCID：0000-0001-7152-0757），医学博士、二级教授、一级主任医师、博士研究生导师，研究方向为外科学、异种移植，Email：wayne0108@126.com

中图分类号: R617, Q527+.5
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- 被引次数: 0
出版历程
- 收稿日期: 2023-04-30
- 录用日期: 2023-07-10
- 网络出版日期: 2023-07-20
- 刊出日期: 2023-09-15

Transmission of porcine endogenous retrovirus in xenotransplantation

1.
Transplantation Institute, the Second Affiliated Hospital of Hainan Medical University, Hainan 570216, China

More Information

Corresponding author: Wang Yi, Email:wayne0108@126.com

摘要

摘要: 器官移植是治疗各类终末期疾病最有效的手段，为了解决器官移植中供体短缺的问题，人们开始探究异种移植的可能。猪是异种器官移植常见的供体来源之一，猪器官作为连接两个物种间的桥梁，其携带的病毒有可能在物种间传播并存在引起人畜共患病的风险。猪内源性逆转录病毒（PERV）整合在基因组中，是一种跨物种传播的逆转录病毒。本文介绍了PERV传播特性的影响因素、PERV及其重组病毒的传播风险以及异种移植试验中PERV的检测与传播风险评估，以期为缓解器官移植供体严重短缺的现状，推动异种移植技术的发展提供参考。
- 异种移植 /
- 猪内源性逆转录病毒 /
- 器官短缺 /
- 转基因 /
- 传播特性 /
- 人畜共患病 /
- 免疫缺陷 /
- 感染
Abstract: Organ transplantation is the most effective treatment for various types of end-stage diseases. To resolve the problem of donor shortage in organ transplantation, the possibility of xenotransplantation has been gradually explored by surgeons. Pig is one of the common donor sources for xenotransplantation. As a bridge between two species, the viruses carried by pig organs may be transmitted between species and cause the risk of zoonosis. Porcine endogenous retrovirus (PERV) is integrated into the genome, which is a category of retrovirus featuring cross-species transmission. In this article, the influencing factors of transmission characteristics of PERV, the transmission risk of PERV and its recombinant virus, and the detection and transmission risk assessment of PERV in xenotransplantation test were reviewed, aiming to provide reference for alleviating severe shortage of donor organs and driving the advancement of xenotransplantation technologies.
- Xenotransplantation /
- Porcine endogenous retrovirus /
- Organ shortage /
- Transgene /
- Transmission characteristics /
- Zoonosis /
- Immunodeficiency /
- Infection

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参考文献(43)

[1]	OPTN/SRTR 2020 annual data report: preface[J]. Am J Transplant, 2022, 22 (Suppl 2): 1-10. DOI: 10.1111/ajt.16975.
[2]	WANG Y, LEI T, WEI L, et al. Xenotransplantation in China: present status[J]. Xenotransplantation, 2019, 26(1): e12490. DOI: 10.1111/xen.12490.
[3]	COZZI E, SCHNEEBERGER S, BELLINI MI, et al. Organ transplants of the future: planning for innovations including xenotransplantation[J]. Transpl Int, 2021, 34(11): 2006-2018. DOI: 10.1111/tri.14031.
[4]	FISCHER K, SCHNIEKE A. Xenotransplantation becoming reality[J]. Transgenic Res, 2022, 31(3): 391-398. DOI: 10.1007/s11248-022-00306-w.
[5]	NIU D, MA X, YUAN T, et al. Porcine genome engineering for xenotransplantation[J]. Adv Drug Deliv Rev, 2021, 168: 229-245. DOI: 10.1016/j.addr.2020.04.001.
[6]	张玄, 王琳, 张洪涛, 等. 多基因编辑猪-猴心脏、肝脏、肾脏移植临床前研究初步报道[J]. 器官移植, 2021, 12(1): 51-56. DOI: 10.3969/j.issn.1674-7445.2021.01.008. ZHANG X, WANG L, ZHANG HT, et al. Preliminary report of a preclinical study of multigene-edited pig-monkey heart, liver, and kidney transplantation [J]. Organ Transplant, 2021, 12(1): 51-56. DOI: 10.3969/j.issn.1674-7445.2021.01.008.
[7]	DENNER J. Porcine endogenous retroviruses and xenotransplantation, 2021 [J]. Viruses, 2021, 13(11): 2156. DOI: 10.3390/v13112156.
[8]	COOPER DKC, HARA H, IWASE H, et al. Pig kidney xenotransplantation: progress toward clinical trials [J]. Clin Transplant, 2021, 35(1): e14139. DOI: 10.1111/ctr.14139.
[9]	PIERSON RN 3RD. Progress toward pig-to-human xenotransplantation[J]. N Engl J Med, 2022, 386(20): 1871-1873. DOI: 10.1056/NEJMp2118019.
[10]	GRIFFITH BP, GOERLICH CE, SINGH AK, et al. Genetically modified porcine-to-human cardiac xenotransplantation [J]. N Engl J Med, 2022, 387(1): 35-44. DOI: 10.1056/NEJMoa2201422.
[11]	马玲, 钟华, 秦树英, 等. 广西巴马小型猪内源性反转录病毒整合后传代次数对HEK293细胞中HERV-W表达和变异的影响[J]. 中国兽医学报, 2020, 40(10): 1918-1923. DOI: 10.16303/j.cnki.1005-4545.2020.10.05. MA L, ZHONG H, QIN SY, et al. Effects of HEK293-PERV-BM passages on the expression and variation of HERV-W in HEK293 cells[J]. Chin J Vet Sci, 2020, 40(10): 1918-1923. DOI: 10.16303/j.cnki.1005-4545.2020.10.05.
[12]	FISHMAN JA. Risks of infectious disease in xenotransplantation[J]. N Engl J Med, 2022, 387(24): 2258-2267. DOI: 10.1056/NEJMra2207462.
[13]	CARRIER AN, VERMA A, MOHIUDDIN M, et al. Xenotransplantation: a new era[J]. Front Immunol, 2022, 13: 900594. DOI: 10.3389/fimmu.2022.900594.
[14]	MEIER RPH, LONGCHAMP A, MOHIUDDIN M, et al. Recent progress and remaining hurdles toward clinical xenotransplantation[J]. Xenotransplantation, 2021, 28(3): e12681. DOI: 10.1111/xen.12681.
[15]	VAN DER LAAN LJ, LOCKEY C, GRIFFETH BC, et al. Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice[J]. Nature, 2000, 407(6800): 90-94. DOI: 10.1038/35024089.
[16]	SONG M, FITCH ZW, SAMY KP, et al. Coagulation, inflammation, and CD46 transgene expression in neonatal porcine islet xenotransplantation[J]. Xenotransplantation, 2021, 28(3): e12680. DOI: 10.1111/xen.12680.
[17]	CARVALHO-OLIVEIRA M, VALDIVIA E, BLASCZYK R, et al. Immunogenetics of xenotransplantation[J]. Int J Immunogenet, 2021, 48(2): 120-134. DOI: 10.1111/iji.12526.
[18]	KONO K, KATAOKA K, YUAN Y, et al. Infectivity assessment of porcine endogenous retrovirus using high-throughput sequencing technologies[J]. Biologicals, 2021, 71: 1-8. DOI: 10.1016/j.biologicals.2021.05.001.
[19]	LE TISSIER P, STOYE JP, TAKEUCHI Y, et al. Two sets of human-tropic pig retrovirus[J]. Nature, 1997, 389(6652): 681-682. DOI: 10.1038/39489.
[20]	DENNER J. Virus safety of xenotransplantation[J]. Viruses, 2022, 14(9): 1926. DOI: 10.3390/v14091926.
[21]	NIU D, WEI HJ, LIN L, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9[J]. Science, 2017, 357(6357): 1303-1307. DOI: 10.1126/science.aan4187.
[22]	WEISS RA. Infection hazards of xenotransplantation: retrospect and prospect[J]. Xenotransplantation, 2018, 25(4): e12401. DOI: 10.1111/xen.12401.
[23]	曾嘉庆, 高岩, 仇相书, 等. 猪逆转录病毒SYBR Green Ⅰ荧光定量PCR检测方法的建立及应用[J]. 中国病原生物学杂志, 2022, 17(1): 26-30. DOI: 10.13350/j.cjpb.220107. ZENG JQ, GAO Y, QIU XS, et al. Establishment and application of a quantitative PCR assay for porcine retrovirus SYBR GreenI fluorescence [J]. Chin J Pathog Biol, 2022, 17(1): 26-30. DOI: 10.13350/j.cjpb.220107.
[24]	冯天悦, KAMAL SHAH, 张文立, 等. 猪内源性逆转录病毒在3种不同品系猪中的分布及序列特征研究[J]. 中国预防兽医学报, 2022, 44(11): 1141-1148, 1168. DOI: 10.3969/j.issn.1008-0589.202201027. FENG TY, KAMAL S, ZHANG WL, et al. Distribution and sequence characteristics of porcine endogenous retroviruses in three different breeds of pigs[J]. Chin J Prev Vet Med, 2022, 44(11): 1141-1148, 1168. DOI: 10.3969/j.issn.1008-0589.202201027.
[25]	DENNER J, TÖNJES RR. Infection barriers to successful xenotransplantation focusing on porcine endogenous retroviruses[J]. Clin Microbiol Rev, 2012, 25(2): 318-343. DOI: 10.1128/CMR.05011-11.
[26]	范瑞, 贾俊婷, 钟亚迪, 等. 五指山小型猪不同器官内猪内源性反转录病毒的存在与表达[J]. 生物技术通讯, 2018, 29(1): 50-54. DOI: 10.3969/j.issn.1009-0002.2018.01.010. FAN R, JIA JT, ZHONG YD, et al. Presence and expression of swine endogenous retrovirus in different organs of Wuzhishan minipigs [J]. Biotechnol Commun, 2018, 29(1): 50-54. DOI: 10.3969/j.issn.1009-0002.2018.01.010.
[27]	白少川, 张乐超, 葛琳涵, 等. 内源性逆转录病毒的转录表达与宿主功能关系的研究进展[J]. 畜牧兽医学报, 2021, 52(8): 2107-2114. DOI: 10.11843/j.issn.0366-6964.2021.08.004. BAI SC, ZHANG LC, GE LH, et al. Research progress of relation between transcriptional expression of endogenous retrovirus and host function[J]. Acta Vet Et Zootech Sin, 2021, 52(8): 2107-2114. DOI: 10.11843/j.issn.0366-6964.2021.08.004.
[28]	UEDA MT, KRYUKOV K, MITSUHASHI S, et al. Comprehensive genomic analysis reveals dynamic evolution of endogenous retroviruses that code for retroviral-like protein domains[J]. Mob DNA, 2020, 11: 29. DOI: 10.1186/s13100-020-00224-w.
[29]	XUE B, SECHI LA, KELVIN DJ. Human endogenous retrovirus K (HML-2) in health and disease[J]. Front Microbiol, 2020, 11: 1690. DOI: 10.3389/fmicb.2020.01690.
[30]	崔杰. 病毒如何与人类共进化——内源性逆转录病毒的秘密[J]. 科学(上海), 2020, 72(3): 50-53. DOI: 10.3969/j.issn.0368-6396.2020.03.012. CUI J. How did viruses co-evolve with humans——the secret of endogenous retroviruses [J]. Science (Shanghai), 2020, 72 (3): 50-53. DOI: 10.3969/j.issn.0368-6396.2020.03.012.
[31]	蒋鸿涛, 李涛, 何松哲, 等. 基因修饰猪-非人灵长类动物异种肾移植面临的问题及挑战[J]. 器官移植, 2022, 13(6): 810-817. DOI: 10.3969/j.issn.1674-7445.2022.06.018. JIANG HT, LI T, HE SZ, et al. Problems and challenges of genetically modified pig to non-human primate kidney xenotransplantation[J]. Organ Transplant, 2022, 13(6): 810-817. DOI: 10.3969/j.issn.1674-7445.2022.06.018.
[32]	PATIENCE C, TAKEUCHI Y, WEISS RA. Infection of human cells by an endogenous retrovirus of pigs[J]. Nat Med, 1997, 3(3): 282-286. DOI: 10.1038/nm0397-282.
[33]	BACH FH, FINEBERG HV. Call for moratorium on xenotransplants[J]. Nature, 1998, 391(6665): 326. DOI: 10.1038/34766.
[34]	PARADIS K, LANGFORD G, LONG Z, et al. Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. the XEN 111 Study Group[J]. Science, 1999, 285(5431): 1236-1241. DOI: 10.1126/science.285.5431.1236.
[35]	邱艳, 陶开山, 李霄, 等. 猪内源性反转录病毒在异种移植中的研究进展[J/CD]. 实用器官移植电子杂志, 2018, 6(5): 405-408. DOI: 10.3969/j.issn.2095-5332.2018.05.016. QIU Y, TAO KS, LI X, et al. Progress of porcine endogenous retrovirus in xenotransplantation [J/CD]. Pract J Organ Transplant (Electr Vers), 2018, 6(5): 405-408. DOI: 10.3969/j.issn.2095-5332.2018.05.016.
[36]	YANG YG, WOOD JC, LAN P, et al. Mouse retrovirus mediates porcine endogenous retrovirus transmission into human cells in long-term human-porcine chimeric mice[J]. J Clin Invest, 2004, 114(5): 695-700. DOI: 10.1172/JCI21946.
[37]	许皓, 张玄, 窦科峰. 异种移植临床试验的有关问题[J]. 中华外科杂志, 2022, 60(10): 888-893. DOI: 10.3760/cma.j.cn112139-20220626-00286. XU H, ZHANG X, DOU KF. Issues related to clinical xenograft trials [J]. Chin J Surg, 2022, 60(10): 888-893. DOI: 10.3760/cma.j.cn112139-20220626-00286.
[38]	YOON CH, CHOI HJ, KIM MK. Corneal xenotransplantation: where are we standing? [J]. Prog Retin Eye Res, 2021, 80: 100876. DOI: 10.1016/j.preteyeres.2020.100876.
[39]	PISANO MP, GRANDI N, TRAMONTANO E. High-throughput sequencing is a crucial tool to investigate the contribution of human endogenous retroviruses (HERVs) to human biology and development[J]. Viruses, 2020, 12(6): 633. DOI: 10.3390/v12060633.
[40]	KRÜGER L, STILLFRIED M, PRINZ C, et al. Copy number and prevalence of porcine endogenous retroviruses (PERVs) in German wild boars[J]. Viruses, 2020, 12(4): 419. DOI: 10.3390/v12040419.
[41]	KRÜGER L, BÖTTGER J, HUANG CA, et al. Absence of porcine endogenous retrovirus (PERV) production from pig lymphoma cell lines[J]. Virus Res, 2021, 295: 198286. DOI: 10.1016/j.virusres.2020.198286.
[42]	DENNER J, SCOBIE L. Are there better assays to evaluate the risk of transmission of porcine endogenous retroviruses (PERVs) to human cells? [J]. Xenotransplantation, 2019, 26(4): e12510. DOI: 10.1111/xen.12510.
[43]	NEGRI A, WILSON L. Future systems of xenotransplantation: melding historical and bioethical methodology[J]. Cell Transplant, 2023, 32: 9636897231170510. DOI: 10.1177/09636897231170510.