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通过体细胞核移植传播致病病毒的风险:对异种移植的影响。

Risk of pathogenic virus transmission by somatic cell nuclear transfer: implications for xenotransplantation.

作者信息

Denner Joachim

机构信息

Institute of Virology, Free University, Berlin, Germany.

出版信息

Biol Reprod. 2022 Sep 12;107(3):717-722. doi: 10.1093/biolre/ioac120.

DOI:10.1093/biolre/ioac120
PMID:35699429
Abstract

Using somatic cell nuclear transfer for the generation of cloned and transgenic animals bears the risk of transmission of viruses, either by the oocyte or by the introduced donor cell. There is evidence that the zona pellucida (ZP) surrounding the oocyte prevents virus infection; however, virus infections despite intact ZP were reported. Furthermore, the protective ZP has to be penetrated to place the somatic cell in the oocyte's perivitelline space during SCNT. Transmission of viruses also represents a severe problem during in vitro fertilization (IVF). Genetically modified and IVF-produced pigs serve as an important biomedical model for numerous diseases and it is important to evaluate whether infections of the model animals can falsify the research data. Of special significance is this topic in the case of xenotransplantation using genetically modified pigs as donor animals, because transmission of porcine viruses may be harmful to the human recipient. This was repeatedly demonstrated in preclinical pig to non-human primate trials. Therefore, donor pigs, oocytes used for SCNT, and genetically modified donor cells should be screened for potentially zoonotic viruses when creating genetically modified pigs designed for xenotransplantation.

摘要

利用体细胞核移植技术生成克隆动物和转基因动物存在病毒传播风险,病毒可通过卵母细胞或导入的供体细胞传播。有证据表明,卵母细胞周围的透明带(ZP)可防止病毒感染;然而,也有报道称尽管透明带完整,但仍发生了病毒感染。此外,在体细胞核移植过程中,必须穿透保护性的透明带才能将体细胞置于卵母细胞的卵周隙中。在体外受精(IVF)过程中,病毒传播也是一个严重问题。转基因和体外受精产生的猪是许多疾病的重要生物医学模型,评估模型动物的感染是否会伪造研究数据很重要。在使用转基因猪作为供体动物进行异种移植的情况下,这个问题具有特殊意义,因为猪病毒的传播可能对人类受体有害。这在临床前猪到非人类灵长类动物的试验中得到了反复证明。因此,在创建用于异种移植的转基因猪时,应对供体猪、用于体细胞核移植的卵母细胞和转基因供体细胞进行潜在人畜共患病毒的筛查。

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引用本文的文献

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Front Vet Sci. 2024 Feb 2;11:1336005. doi: 10.3389/fvets.2024.1336005. eCollection 2024.
2
The prevention strategies of swine viruses related to xenotransplantation.与异种移植相关的猪病毒的预防策略。
Virol J. 2023 Jun 13;20(1):121. doi: 10.1186/s12985-023-02090-3.
3
Detection of porcine cytomegalovirus, a roseolovirus, in pig ovaries and follicular fluid: implications for somatic cells nuclear transfer, cloning and xenotransplantation.
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Virol J. 2023 Jan 27;20(1):15. doi: 10.1186/s12985-023-01975-7.
4
How, where and when to screen for porcine cytomegalovirus (PCMV) in donor pigs for xenotransplantation.如何、何地以及何时对异种移植供体猪进行猪巨细胞病毒(PCMV)筛查。
Sci Rep. 2022 Dec 13;12(1):21545. doi: 10.1038/s41598-022-25624-1.
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