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: Li, Jiayu 1 ; Xing, Huiyan 1 ; Liu, Kai 1 ; Fan, Ninglin 1 ; Xu, Kaixiang 1 ; Zhao, Heng 1 ; Jiao, Deling 1 ; Wei, Taiyun 1 ; Cheng, Wenjie 1 ; Guo, Jianxiong 1 ; Zhang, Xiong 1 ; Zhu, Feiyan 1 ; Bu, Zhigao 5 ; Zhao, Dongming 5 ; Wang, Wen 6 ; Wei, Hong-Jiang 1 ;
作者机构: 1.Yunnan Agr Univ, Key Lab Porcine Gene Editing & Xenotransplantat Yu, Kunming 650201, Peoples R China
2.Yunnan Agr Univ, Xenotransplantat Engn Res Ctr Yunnan Prov, Kunming 650201, Peoples R China
3.Yunnan Agr Univ, Coll Vet Med, Kunming 650201, Peoples R China
4.Yunnan Agr Univ, Coll Anim Sci & Technol, Kunming 650201, Peoples R China
5.Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Anim Dis Control & Prevent, Natl High Containment Facil Anim Dis Control & Pre, Harbin 150069, Peoples R China
6.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Peoples R China
关键词: pig; African swine fever virus; TRBV27 gene; complementarity determining region 1; gene editing
期刊名称:MICROORGANISMS ( 影响因子:4.1; 五年影响因子:4.5 )
ISSN:
年卷期: 2024 年 12 卷 6 期
页码:
收录情况: SCI
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 degrees 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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