Shen Huan-Huan, Zhao Qin, Wen Yi-Ping, Wu Rui, Du Sen-Yan, Huang Xiao-Bo, Wen Xin-Tian, Cao San-Jie, Zeng Lei, Yan Qi-Gui
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 610000, Sichuan Province, China.
College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan Province, China.
iScience. 2023 Jul 22;26(8):107450. doi: 10.1016/j.isci.2023.107450. eCollection 2023 Aug 18.
Porcine reproductive and respiratory syndrome virus (PRRSV) poses a severe threat to the health of pigs globally. Host factors play a critical role in PRRSV replication. Using PRRSV as a model for genome-scale CRISPR knockout (KO) screening, we identified a host factor critical to PRRSV infection: sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B). Our findings show that SMPDL3B restricted PRRSV attachment, entry, replication, and secretion and that its depletion significantly inhibited PRRSV proliferation, indicating that SMPDL3B plays a positive role in PRRSV replication. Our data also show that SMPDL3B deficiency resulted in an accumulation of intracellular lipid droplets (LDs). The expression level of key genes (ACC, SCD-1, and FASN) involved in lipogenesis was increased, whereas the fundamental lipolysis gene, ATGL, was inhibited when SMPDL3B was knocked down. Overall, our findings suggest that SMPDL3B deficiency can effectively inhibit viral infection through the modulation of lipid metabolism.
猪繁殖与呼吸综合征病毒（PRRSV）对全球猪的健康构成严重威胁。宿主因子在PRRSV复制中起关键作用。以PRRSV作为全基因组规模CRISPR敲除（KO）筛选的模型，我们鉴定出一个对PRRSV感染至关重要的宿主因子：鞘磷脂磷酸二酯酶酸性样3B（SMPDL3B）。我们的研究结果表明，SMPDL3B限制PRRSV的附着、进入、复制和分泌，其缺失显著抑制PRRSV增殖，表明SMPDL3B在PRRSV复制中起积极作用。我们的数据还表明，SMPDL3B缺陷导致细胞内脂滴（LDs）积累。当SMPDL3B被敲低时，参与脂肪生成的关键基因（ACC、SCD - 1和FASN）的表达水平升高，而基本的脂肪分解基因ATGL受到抑制。总体而言，我们的研究结果表明，SMPDL3B缺陷可通过调节脂质代谢有效抑制病毒感染。
