Jia Meiyu, Sun Mingxia, Tang Yan-Dong, Zhang Yu-Yuan, Wang Haiwei, Cai Xuehui, Meng Fandan
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Front Vet Sci. 2022 Apr 8;9:840655. doi: 10.3389/fvets.2022.840655. eCollection 2022.
Senecavirus A (SVA), an important member of the family, causes vesicular disease in pigs. Here, we generated an EGFP-expressing recombinant SVA re-SVA-EGFP, which exhibited similar growth kinetics to its parental virus. The reporter SVA was used to study the role of pig ANTXR1 (pANTXR1) in SVA infection in a porcine alveolar macrophage cell line (PAM-Tang cells). Knockdown of the pANTXR1 significantly reduced SVA infection and replication in PAM-Tang cells, while re-expression of the pANTXR1 promoted the cell susceptibility to SVA infection. The results indicated that pANTXR1 is a crucial receptor mediating SVA infection. Subsequently, the viral endocytosis pathways for SVA entry into pig cells were investigated and the results showed that cholesterol played an essential role in receptor-mediated SVA entry. Together, these results demonstrated that SVA entered into host cells through the pANTXR1-mediated cholesterol pathway. Our findings provide potential targets to develop antiviral drugs for the prevention of SVA infection in the pig population.
A组赛内卡病毒(SVA)是该病毒家族的重要成员,可引起猪的水疱性疾病。在此,我们构建了一种表达增强型绿色荧光蛋白(EGFP)的重组SVA,即re-SVA-EGFP,其生长动力学与其亲本病毒相似。该报告基因SVA用于研究猪炭疽毒素受体1(pANTXR1)在猪肺泡巨噬细胞系(PAM-Tang细胞)的SVA感染中的作用。敲低pANTXR1可显著降低SVA在PAM-Tang细胞中的感染和复制,而pANTXR1的重新表达则促进细胞对SVA感染的易感性。结果表明,pANTXR1是介导SVA感染的关键受体。随后,对SVA进入猪细胞的病毒内吞途径进行了研究,结果表明胆固醇在受体介导的SVA进入过程中起重要作用。总之,这些结果表明SVA通过pANTXR1介导的胆固醇途径进入宿主细胞。我们的研究结果为开发预防猪群SVA感染的抗病毒药物提供了潜在靶点。