Downregulation of miR-296-3p by highly pathogenic porcine reproductive and respiratory syndrome virus activates the IRF1/TNF-α signaling axis in porcine alveolar macrophages

• Published in: Archives of virology 2021-02, Vol.166 (2), p.511-519
• Main Authors: Zhang, Yanbing, Xiang, Xiao, Lu, Yan, Li, Hui, Wahaab, Abdul, Sharma, Mona, Liu, Ke, Wei, Jianchao, Li, Zongjie, Shao, Donghua, Li, Beibei, Ma, Zhiyong, Qiu, Yafeng
• Format: Article
• Language: English
• Subjects: Alveoli; Animal diseases; Animals; Biomedical and Life Sciences; Biomedicine; Cell Line; Chlorocebus aethiops; Down-Regulation - genetics; Farms; Gene Expression Profiling - methods; HEK293 Cells; Host-Pathogen Interactions - genetics; Humans; Infections; Infectious Diseases; Inflammation; Interferon regulatory factor 1; Interferon Regulatory Factor-1 - genetics; Macrophages; Macrophages, Alveolar - virology; Medical Microbiology; MicroRNAs - genetics; miRNA; Original Article; Porcine Reproductive and Respiratory Syndrome - genetics; Porcine Reproductive and Respiratory Syndrome - virology; Porcine respiratory and reproductive syndrome virus - physiology; Regulatory sequences; Replication; Signal Transduction - genetics; Swine - genetics; Swine - virology; Transcriptome - genetics; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-α; Viral infections; Virology; Virus Replication - genetics
• ISSN: 0304-8608; 1432-8798
• DOI: 10.1007/s00705-020-04921-y

Porcine reproductive and respiratory syndrome virus (PRRSV, species Betaarterivirus suid 1 or 2 ) is a major pathogen affecting pigs on farms throughout the world. miR-296-3p is a multifunctional microRNA involved in the regulation of the inflammatory response in mice and humans. However, little is known about the biological functions of miR-296-3p in pigs. In this study, we used a highly pathogenic PRRSV-2 (species Betaarterivirus suid 2 ) strain to show that PRRSV infection robustly downregulates the expression of miR-296-3p in porcine alveolar macrophages (PAMs). Furthermore, we demonstrated that overexpression of miR-296-3p increases the replication of highly pathogenic (HP)-PRRSV in PAMs. Notably, the overexpression of miR-296-3p inhibited the induction of TNF-α, even with increased viral replication, compared with that in the HP-PRRSV-infected control group. We also demonstrated that miR-296-3p targets IRF1-facilitated viral infection and modulates the expression of TNF-α in PAMs during HP-PRRSV infection and that IRF1 regulates the expression of TNF-α by activating the TNF promoter via IRF1 response elements. In summary, these findings show that HP-PRRSV infection activates the IRF1/TNF-α signaling axis in PAMs by downregulating host miR-296-3p. This extends our understanding of the inflammatory response induced by HP-PRRSV infection.