Preliminary Research on the Mechanism of SOCS3 Negatively Regulating the Expression of Interferons Induced by Influenza Virus

PENG Benqun; HU Jingyun; MAO Yanan; WANG Shulin; WANG Jiajun; CHEN Mengying; YOU Dongxue; WANG Song

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PENG B Q, HU J Y, MAO Y N, et al. Preliminary Research on the Mechanism of SOCS3 Negatively Regulating the Expression of Interferons Induced by Influenza Virus [J]. Fujian Journal of Agricultural Sciences，2024，39（X）：1−6

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PENG B Q, HU J Y, MAO Y N, et al. Preliminary Research on the Mechanism of SOCS3 Negatively Regulating the Expression of Interferons Induced by Influenza Virus [J]. Fujian Journal of Agricultural Sciences，2024，39（X）：1−6

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Preliminary Research on the Mechanism of SOCS3 Negatively Regulating the Expression of Interferons Induced by Influenza Virus

PENG Benqun^{1, 2, 3
,},
HU Jingyun^{1, 2, 3},
MAO Yanan^{1, 2},
WANG Shulin^{1, 2},
WANG Jiajun^{1, 3},
CHEN Mengying^{1, 3},
YOU Dongxue^{1, 3},
WANG Song^{1, 2, 3
,
,}

1.
College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, , Fujian　350002, China
2.
Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, Fuzhou, Fujian　350002, China
3.
Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, Fuzhou, Fujian　350002, China

Received Date: 2024-01-03
Rev Recd Date: 2024-02-29

Available Online: 2024-03-28

Abstract

Abstract

Objective The regulatory impact of SOCS3 on the interferon signaling pathway during influenza virus infection was studied. Method The A549 cell lines with SOCS3 overexpression and knockdown were constructed using lentivirus infection and siRNA technology, respectively. Subsequently, these cell lines, along with control cell lines, were infected with influenza virus. Samples were collected at different time points to assess the expression and activation of crucial molecules within the interferon signaling pathway using RT-PCR and Western blot analysis. Result The findings demonstrated a decrease in expression levels of type I interferon IFN-β and type III interferons IL-28 and IL-29 following the overexpression of SOCS3 in cells. Conversely, the expression levels of IFN-β, IL-28, and IL-29 were observed to increase upon the knockdown of SOCS3 expression. Subsequent investigations indicated that the overexpression of SOCS3 suppressed the expression of interferon regulatory factor IRF7, as well as pattern recognition receptors RIG-I, MDA5, and TLR3 responsible for detecting influenza virus RNA. Additionally, the phosphorylation level of STAT1 after virus infection was detected, and the results showed that overexpression of SOCS3 in cells inhibited the phosphorylation of STAT1 induced by influenza virus, while knocking down the expression of SOCS3 increased the phosphorylation level of STAT1. Conclusion Upon influenza virus infection, SOCS3 down-regulated the mRNA expression of pattern recognition receptors and interferon regulatory factor, inhibited the production of type I and III interferons, as well as the activation of STAT1. This ultimately led to the blocking of interferon signal transmission.
- influenza virus,
- SOCS3,
- interferon,
- innate immunity,
- STAT1

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References(19)

References

[1]	HUTCHINSON E C. Influenza virus [J]. Trends in Microbiology, 2018, 26(9): 809−810. doi: 10.1016/j.tim.2018.05.013
[2]	UYEKI T M, HUI D S, ZAMBON M, et al. Influenza [J]. Lancet, 2022, 400(10353): 693−706. doi: 10.1016/S0140-6736(22)00982-5
[3]	GORAYA M U, ZAIGHUM F, SAJJAD N, et al. Web of interferon stimulated antiviral factors to control the influenza A viruses replication [J]. Microbial Pathogenesis, 2020, 139: 103919. doi: 10.1016/j.micpath.2019.103919
[4]	WONG P T, GOFF P H, SUN R J, et al. Combined intranasal nanoemulsion and RIG-I activating RNA adjuvants enhance mucosal, humoral, and cellular immunity to influenza virus [J]. Molecular Pharmaceutics, 2021, 18(2): 679−698. doi: 10.1021/acs.molpharmaceut.0c00315
[5]	MA W, HUANG G, WANG Z, et al. IRF7: Role and regulation in immunity and autoimmunity [J]. Frontiers in Immunology, 2023, 14: 1236923. doi: 10.3389/fimmu.2023.1236923
[6]	YAO D D, BAO L L, LI F D, et al. H1N1 influenza virus dose dependent induction of dysregulated innate immune responses and STAT1/3 activation are associated with pulmonary immunopathological damage [J]. Virulence, 2022, 13(1): 1558−1572. doi: 10.1080/21505594.2022.2120951
[7]	HALLER O, KOCHS G. Mx genes: Host determinants controlling influenza virus infection and trans-species transmission [J]. Human Genetics, 2020, 139(6): 695−705.
[8]	周斌, 万少兵, 王瑛, 等. SOCS3通过调控JAK2/STAT3信号通路改善急性肺损伤 [J]. 山西医科大学学报, 2023, 54(6):778−784. ZHOU B, WAN S B, WANG Y, et al. SOCS3 improves acute lung injury by regulating JAK2/STAT3 signaling pathway [J]. Journal of Shanxi Medical University, 2023, 54(6): 778−784. (in Chinese)
[9]	SIMS N A. The JAK1/STAT3/SOCS3 axis in bone development, physiology, and pathology [J]. Experimental & Molecular Medicine, 2020, 52: 1185−1197.
[10]	LIU S S, YAN R X, CHEN B, et al. Influenza virus-induced robust expression of SOCS3 contributes to excessive production of IL-6 [J]. Frontiers in Immunology, 2019, 10: 1843. doi: 10.3389/fimmu.2019.01843
[11]	SUN Y P, JIANG J W, PO T E, et al. IFN-λ: A new spotlight in innate immunity against influenza virus infection [J]. Protein & Cell, 2018, 9(10): 832−837.
[12]	BIONDO C, LENTINI G, BENINATI C, et al. The dual role of innate immunity during influenza [J]. Biomedical Journal, 2019, 42(1): 8−18. doi: 10.1016/j.bj.2018.12.009
[13]	HUANG B Z, CHEN H P, ZHENG Y B. MiR-103/miR-107 inhibits enterovirus 71 replication and facilitates type I interferon response by regulating SOCS3/STAT3 pathway [J]. Biotechnology Letters, 2021, 43(7): 1357−1369. doi: 10.1007/s10529-021-03115-z
[14]	YAKASS M B, FRANCO D, QUAYE O. Suppressors of cytokine signaling and protein inhibitors of activated signal transducer and activator of transcriptions As therapeutic targets in flavivirus infections [J]. Journal of Interferon & Cytokine Research, 2020, 40(1): 1−18.
[15]	LI L, WU H Y, LI Q M, et al. SOCS3-deficient lung epithelial cells uptaking neutrophil-derived SOCS3 worsens lung influenza infection [J]. Molecular Immunology, 2020, 125: 51−62. doi: 10.1016/j.molimm.2020.06.022
[16]	YANG H, DONG Y R, BIAN Y, et al. The influenza virus PB2 protein evades antiviral innate immunity by inhibiting JAK1/STAT signalling [J]. Nature Communications, 2022, 13: 6288. doi: 10.1038/s41467-022-33909-2
[17]	ZHANG Y L, XU L L, ZHANG Z, et al. Enterovirus D68 infection upregulates SOCS3 expression to inhibit JAK-STAT3 signaling and antagonize the innate interferon response of the host [J]. Virologica Sinica, 2023, 38(5): 755−766. doi: 10.1016/j.virs.2023.08.007
[18]	WANG X W, JIA Y Q, REN J, et al. Newcastle disease virus nonstructural V protein upregulates SOCS3 expression to facilitate viral replication depending on the MEK/ERK pathway [J]. Frontiers in Cellular and Infection Microbiology, 2019, 9: 317. doi: 10.3389/fcimb.2019.00317
[19]	XIE J Y, WANG M S, CHENG A C, et al. DHAV-1 inhibits type I interferon signaling to assist viral adaption by increasing the expression of SOCS3 [J]. Frontiers in Immunology, 2019, 10: 731. doi: 10.3389/fimmu.2019.00731