PMID- 34056880 OWN - NLM STAT- MEDLINE DCOM- 20210913 LR - 20210913 IS - 1976-555X (Electronic) IS - 1229-845X (Print) IS - 1229-845X (Linking) VI - 22 IP - 3 DP - 2021 May TI - Role of IFNLR1 gene in PRRSV infection of PAM cells. PG - e39 LID - 10.4142/jvs.2021.22.e39 [doi] LID - e39 AB - BACKGROUND: Interferon lambda receptor 1 (IFNLR1) is a type II cytokine receptor that clings to interleukins IL-28A, IL29B, and IL-29 referred to as type III IFNs (IFN-lambdas). IFN-lambdas act through the JAK-STAT signaling pathway to exert antiviral effects related to preventing and curing an infection. Although the immune function of IFN-lambdas in virus invasion has been described, the molecular mechanism of IFNLR1 in that process is unclear. OBJECTIVES: The purpose of this study was to elucidate the role of IFNLR1 in the pathogenesis and treatment of porcine reproductive and respiratory syndrome virus (PRRSV). METHODS: The effects of IFNLR1 on the proliferation of porcine alveolar macrophages (PAMs) during PRRSV infection were investigated using interference and overexpression methods. RESULTS: In this study, the expressions of the IFNLR1 gene in the liver, large intestine, small intestine, kidney, and lung tissues of Dapulian pigs were significantly higher than those in Landrace pigs. It was determined that porcine IFNLR1 overexpression suppresses PRRSV replication. The qRT-PCR results revealed that overexpression of IFNLR1 upregulated antiviral and IFN-stimulated genes. IFNLR1 overexpression inhibits the proliferation of PAMs and upregulation of p-STAT1. By contrast, knockdown of IFNLR1 expression promotes PAMs proliferation. The G0/G1 phase proportion in IFNLR1-overexpressing cells increased, and the opposite change was observed in IFNLR1-underexpressing cells. After inhibition of the JAK/STAT signaling pathway, the G2/M phase proportion in the IFNLR1-overexpressing cells showed a significant increasing trend. In conclusion, overexpression of IFNLR1 induces activation of the JAK/STAT pathway, thereby inhibiting the proliferation of PAMs infected with PRRSV. CONCLUSION: Expression of the IFNLR1 gene has an important regulatory role in PRRSV-infected PAMs, indicating it has potential as a molecular target in developing a new strategy for the treatment of PRRSV. CI - (c) 2021 The Korean Society of Veterinary Science. FAU - Qin, Ming AU - Qin M AUID- ORCID: 0000-0003-2212-2626 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, Tai' an City, Shandong Province 271018, China. FAU - Chen, Wei AU - Chen W AUID- ORCID: 0000-0002-2901-5156 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, Tai' an City, Shandong Province 271018, China. FAU - Li, Zhixin AU - Li Z AUID- ORCID: 0000-0002-0218-1680 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, Tai' an City, Shandong Province 271018, China. FAU - Wang, Lixue AU - Wang L AUID- ORCID: 0000-0001-9704-1527 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, Tai' an City, Shandong Province 271018, China. FAU - Ma, Lixia AU - Ma L AUID- ORCID: 0000-0001-9475-7650 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, Tai' an City, Shandong Province 271018, China. FAU - Geng, Jinhong AU - Geng J AUID- ORCID: 0000-0002-5784-9238 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, Tai' an City, Shandong Province 271018, China. FAU - Zhang, Yu AU - Zhang Y AUID- ORCID: 0000-0002-4326-6031 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, Tai' an City, Shandong Province 271018, China. FAU - Zhao, Jing AU - Zhao J AUID- ORCID: 0000-0002-4909-8550 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, Tai' an City, Shandong Province 271018, China. FAU - Zeng, Yongqing AU - Zeng Y AUID- ORCID: 0000-0002-0740-2470 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, Tai' an City, Shandong Province 271018, China. yqzeng@sdau.edu.cn. LA - eng GR - 2020LZGC012/Agricultural Animal Breeding Project of Shandong Province/China GR - SYL2017YSTD12/Shandong "Double Tops" Program/China GR - SDAIT-08-02/Shandong Modern Pig Technology & Industry System Project/China GR - ZR2018BC046/Shandong Provincial Natural Science Foundation/China GR - ZR2019MC053/Shandong Provincial Natural Science Foundation/China PT - Journal Article PL - Korea (South) TA - J Vet Sci JT - Journal of veterinary science JID - 100964185 RN - 0 (Receptors, Interferon) SB - IM MH - Animals MH - Cell Line MH - Macrophages, Alveolar/metabolism/*virology MH - Porcine Reproductive and Respiratory Syndrome/*physiopathology/virology MH - Porcine respiratory and reproductive syndrome virus/*physiology MH - Receptors, Interferon/*metabolism MH - Sus scrofa MH - Swine PMC - PMC8170216 OTO - NOTNLM OT - IFNLR1 OT - PRRSV OT - cell cycle OT - proliferation OT - replication COIS- The authors declare no conflicts of interest. EDAT- 2021/06/01 06:00 MHDA- 2021/09/14 06:00 PMCR- 2021/05/01 CRDT- 2021/05/31 06:42 PHST- 2021/02/04 00:00 [received] PHST- 2021/04/11 00:00 [revised] PHST- 2021/04/15 00:00 [accepted] PHST- 2021/05/31 06:42 [entrez] PHST- 2021/06/01 06:00 [pubmed] PHST- 2021/09/14 06:00 [medline] PHST- 2021/05/01 00:00 [pmc-release] AID - 22.e39 [pii] AID - 10.4142/jvs.2021.22.e39 [doi] PST - ppublish SO - J Vet Sci. 2021 May;22(3):e39. doi: 10.4142/jvs.2021.22.e39.