数字农科院2.0

Dysfunction of Complementarity Determining Region 1 Encoded by T Cell Receptor Beta Variable Gene Is Potentially Associated with African Swine Fever Virus Infection in Pigs

文献类型： 外文期刊

作者： Jiayu Li;Huiyan Xing;Kai Liu;Ninglin Fan;Kaixiang Xu;Heng Zhao;Deling Jiao;Taiyun Wei;Wenjie Cheng;Jianxiong Guo;Xiong Zhang;Feiyan Zhu;Zhigao Bu;Dongming Zhao;Wen Wang;Hong Jiang Wei

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关键词： African swine fever virus;complementarity determining region 1;gene editing;pig;TRBV27 gene

期刊名称： Microorganisms

ISSN： 2076-2607

年卷期： 2024 年 12 卷 6 期

页码：

收录情况： SCIE（2024版）

摘要： The beta T-cell receptor (TRB) expressed by beta T cells is essential for foreign antigen recognition. The TRB locus contains a TRBV family that encodes three complementarity determining regions (CDRs). CDR1 is associated with antigen recognition and interactions with MHC molecules. In contrast to domestic pigs, African suids lack a 284-bp segment spanning exons 1 and 2 of the TRBV27 gene that contains a sequence encoding CDR1. In this study, we used the African swine fever virus (ASFV) as an example to investigate the effect of deleting the TRBV27-encoded CDR1 on the resistance of domestic pigs to exotic pathogens. We first successfully generated TRBV27-edited fibroblasts with disruption of the CDR1 sequence using CRISPR/Cas9 technology and used them as donor cells to generate gene-edited pigs via somatic cell nuclear transfer. The TRBV-edited and wild-type pigs were selected for synchronous ASFV infection. White blood cells were significantly reduced in the genetically modified pigs before ASFV infection. The genetically modified and wild-type pigs were susceptible to ASFV and exhibited typical fevers (>40 °C). However, the TRBV27-edited pigs had a higher viral load than the wild-type pigs. Consistent with this, the gene-edited pigs showed more clinical signs than the wild-type pigs. In addition, both groups of pigs died within 10 days and showed similar severe lesions in organs and tissues. Future studies using lower virulence ASFV isolates are needed to determine the relationship between the TRBV27 gene and ASFV infection in pigs over a relatively long period.

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