DHAV-1 Inhibits Type I Interferon Signaling to Assist Viral Adaption by Increasing the Expression of SOCS3

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2019 Apr 27

PMID 31024559

Citations 8

Authors

Jinyan Xie

Mingshu Wang

Anchun Cheng

Xin-Xin Zhao

Mafeng Liu

Dekang Zhu

Shun Chen

Renyong Jia

Qiao Yang

Ying Wu

Shaqiu Zhang

Yunya Liu

Yanling Yu

Ling Zhang

Xiaoyue Chen

Affiliations

Soon will be listed here.

Abstract

Duck hepatitis A virus type 1 (DHAV-1) is one of the most lethal pathogens in the duck industry. The attenuated vaccine (the CH60 strain) is cultivated through serial passage in chicken embryos and is widely used for the prevention and control of the disease. However, the specific mechanism underlying its adaptation in chicken embryos has not been fully elucidated. In this study, we first infected chicken embryo fibroblasts (CEFs) with the DHAV-1 CH60 strain. The peak of viral proliferation occurred within 36-48 h post-infection. The different DHAV-1 strains significantly induced the expression of IFNα, IFNγ, and Suppressor of cytokine signaling 3 (SOCS3) in CEFs, and we found that SOCS3 overexpression significantly promoted viral replication. Furthermore, SOCS3 overexpression significantly inhibited the expression of IFNα but promoted the expression of IFNγ. In addition, SOCS3 overexpression clearly decreased the mRNA levels of STAT1 and STAT3 in the Janus kinase (JAK)-STAT signaling pathway and inhibited the expression of the antiviral proteins MX1 and OASL. Immune-precipitation assays indicated that SOCS3 and IFNα do not physically interact. Subcellular localization of SOCS3 and IFNα revealed that SOCS3 was mainly located in the nucleus and cytoplasm, while IFNα was located only in the cytoplasm. Co-localization of these two proteins was not observed in the cytoplasm. In conclusion, the DHAV-1 CH60 strain may inhibit the expression of IFNα by increasing the SOCS3 protein and SOCS3 can in turn decrease STAT1 and STAT3 mRNA levels, thereby inhibiting the antiviral protein MX1 and ultimately promoting viral proliferation, indirectly assisting in viral adaptation in chicken embryos.

Citing Articles

RNA-seq and microRNA association analysis to explore the pathogenic mechanism of DHAV-1 infection with DEHs.

Wang W, Li K, Zhang T, Dong H, Liu J Funct Integr Genomics. 2023; 23(2):99.

PMID: 36959488 PMC: 10035973. DOI: 10.1007/s10142-023-01022-2.

Duck hepatitis A virus type 1 mediates cell cycle arrest in the S phase.

Liu Y, Li Y, Wang M, Cheng A, Ou X, Mao S Virol J. 2022; 19(1):111.

PMID: 35761382 PMC: 9235186. DOI: 10.1186/s12985-022-01839-6.

Long Noncoding RNA Expression Rofiles Elucidate the Potential Roles of lncRNA- XR_003496198 in Duck Hepatitis A Virus Type 1 Infection.

Sui N, Zhang R, Jiang Y, Yu H, Xu G, Wang J Front Cell Infect Microbiol. 2022; 12:858537.

PMID: 35531338 PMC: 9074814. DOI: 10.3389/fcimb.2022.858537.

Promotes ALV-J Virus Replication Inhibiting JAK2/STAT3 Phosphorylation During Infection.

Mo G, Fu H, Hu B, Zhang Q, Xian M, Zhang Z Front Cell Infect Microbiol. 2021; 11:748795.

PMID: 34568100 PMC: 8461107. DOI: 10.3389/fcimb.2021.748795.

Duck Hepatitis A Virus Type 1 Induces eIF2α Phosphorylation-Dependent Cellular Translation Shutoff PERK/GCN2.

Liu Y, Cheng A, Wang M, Mao S, Ou X, Yang Q Front Microbiol. 2021; 12:624540.

PMID: 33912143 PMC: 8072014. DOI: 10.3389/fmicb.2021.624540.

References

Bullen D, Darwiche R, Metcalf D, Handman E, Alexander W . Neutralization of interferon-gamma in neonatal SOCS1-/- mice prevents fatty degeneration of the liver but not subsequent fatal inflammatory disease. Immunology. 2001; 104(1):92-8. PMC: 1783280. DOI: 10.1046/j.1365-2567.2001.01294.x. View

Alexander W . Suppressors of cytokine signalling (SOCS) in the immune system. Nat Rev Immunol. 2002; 2(6):410-6. DOI: 10.1038/nri818. View

Kinjyo I, Hanada T, Inagaki-Ohara K, Mori H, Aki D, Ohishi M . SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity. 2002; 17(5):583-91. DOI: 10.1016/s1074-7613(02)00446-6. View

Bode J, Ludwig S, Ehrhardt C, Albrecht U, Erhardt A, Schaper F . IFN-alpha antagonistic activity of HCV core protein involves induction of suppressor of cytokine signaling-3. FASEB J. 2003; 17(3):488-90. DOI: 10.1096/fj.02-0664fje. View

Mbow M, Sarisky R . What is disrupting IFN-alpha's antiviral activity?. Trends Biotechnol. 2004; 22(8):395-9. DOI: 10.1016/j.tibtech.2004.06.002. View

Yang M, Cheng A, Wang M, Xing H . Development and application of a one-step real-time Taqman RT-PCR assay for detection of Duck hepatitis virus type1. J Virol Methods. 2008; 153(1):55-60. DOI: 10.1016/j.jviromet.2008.06.012. View

Takeuchi O, Akira S . Innate immunity to virus infection. Immunol Rev. 2009; 227(1):75-86. PMC: 5489343. DOI: 10.1111/j.1600-065X.2008.00737.x. View

Kim K, Lin W, Tai A, Shao R, Weinberg E, De Sa Borges C . Hepatic SOCS3 expression is strongly associated with non-response to therapy and race in HCV and HCV/HIV infection. J Hepatol. 2009; 50(4):705-11. PMC: 3146466. DOI: 10.1016/j.jhep.2008.12.021. View

Anchun C, Mingshu W, Hongyi X, Dekang Z, Xinran L, Haijuen C . Development and application of a reverse transcriptase polymerase chain reaction to detect Chinese isolates of duck hepatitis virus type 1. J Microbiol Methods. 2009; 77(3):332-6. DOI: 10.1016/j.mimet.2009.02.002. View

10.

Akhtar L, Benveniste E . Viral exploitation of host SOCS protein functions. J Virol. 2010; 85(5):1912-21. PMC: 3067810. DOI: 10.1128/JVI.01857-10. View

11.

Tamiya T, Kashiwagi I, Takahashi R, Yasukawa H, Yoshimura A . Suppressors of cytokine signaling (SOCS) proteins and JAK/STAT pathways: regulation of T-cell inflammation by SOCS1 and SOCS3. Arterioscler Thromb Vasc Biol. 2011; 31(5):980-5. DOI: 10.1161/ATVBAHA.110.207464. View

12.

Inagaki-Ohara K, Kondo T, Ito M, Yoshimura A . SOCS, inflammation, and cancer. JAKSTAT. 2013; 2(3):e24053. PMC: 3772102. DOI: 10.4161/jkst.24053. View

13.

Song C, Yu S, Duan Y, Hu Y, Qiu X, Tan L . Effect of age on the pathogenesis of DHV-1 in Pekin ducks and on the innate immune responses of ducks to infection. Arch Virol. 2013; 159(5):905-14. DOI: 10.1007/s00705-013-1900-7. View

14.

Carow B, Rottenberg M . SOCS3, a Major Regulator of Infection and Inflammation. Front Immunol. 2014; 5:58. PMC: 3928676. DOI: 10.3389/fimmu.2014.00058. View

15.

Liu Y, Zhang Z, Zhao X, Yu R, Zhang X, Wu S . Enterovirus 71 inhibits cellular type I interferon signaling by downregulating JAK1 protein expression. Viral Immunol. 2014; 27(6):267-76. DOI: 10.1089/vim.2013.0127. View

16.

Wen X, Cheng A, Wang M, Jia R, Zhu D, Chen S . Detection, differentiation, and VP1 sequencing of duck hepatitis A virus type 1 and type 3 by a 1-step duplex reverse-transcription PCR assay. Poult Sci. 2014; 93(9):2184-92. DOI: 10.3382/ps.2014-04024. View

17.

Shen Y, Cheng A, Wang M, Chen S, Jia R, Zhu D . Development of an indirect ELISA method based on the VP3 protein of duck hepatitis A virus type 1 (DHAV-1) for dual detection of DHAV-1 and DHAV-3 antibodies. J Virol Methods. 2015; 225:30-4. DOI: 10.1016/j.jviromet.2015.08.016. View

18.

Wen X, Cheng A, Wang M, Jia R, Zhu D, Chen S . Recent advances from studies on the role of structural proteins in enterovirus infection. Future Microbiol. 2015; 10(9):1529-42. DOI: 10.2217/fmb.15.62. View

19.

Sun D, Chen S, Cheng A, Wang M . Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells. Viruses. 2016; 8(3):82. PMC: 4810272. DOI: 10.3390/v8030082. View

20.

Cao J, Ou X, Zhu D, Ma G, Cheng A, Wang M . The 2A2 protein of Duck hepatitis A virus type 1 induces apoptosis in primary cell culture. Virus Genes. 2016; 52(6):780-788. DOI: 10.1007/s11262-016-1364-4. View