Porcine reproductive and respiratory syndrome virus upregulates SMPDL3B to promote viral replication by modulating lipid metabolism

Huan-Huan Shen; Qin Zhao; Yi-Ping Wen; Rui Wu; Sen-Yan Du; Xiao-Bo Huang; Xin-Tian Wen; San-Jie Cao; Lei Zeng; Qi-Gui Yan

doi:10.1016/j.isci.2023.107450

Porcine reproductive and respiratory syndrome virus upregulates SMPDL3B to promote viral replication by modulating lipid metabolism

iScience. 2023 Jul 22;26(8):107450. doi: 10.1016/j.isci.2023.107450. eCollection 2023 Aug 18.

Authors

Affiliations

¹ College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 610000, Sichuan Province, China.
² College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan Province, China.

Abstract

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.

Keywords: Biological sciences; Molecular biology; Molecular physiology; Virology.