Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation

Cellular & Molecular Immunology volume 20, pages 1457–1471 (2023)Cite this article

Subjects

Abstract

The G protein-coupled receptor ADGRE5 (CD97) binds to various metabolites that play crucial regulatory roles in metabolism. However, its function in the antiviral innate immune response remains to be determined. In this study, we report that CD97 inhibits virus-induced type-I interferon (IFN-I) release and enhances RNA virus replication in cells and mice. CD97 was identified as a new negative regulator of the innate immune receptor RIG-I, and RIG-1 degradation led to the suppression of the IFN-I signaling pathway. Furthermore, overexpression of CD97 promoted the ubiquitination of RIG-I, resulting in its degradation, but did not impact its mRNA expression. Mechanistically, CD97 upregulates RNF125 expression to induce RNF125-mediated RIG-I degradation via K48-linked ubiquitination at Lys181 after RNA virus infection. Most importantly, CD97-deficient mice are more resistant than wild-type mice to RNA virus infection. We also found that sanguinarine-mediated inhibition of CD97 effectively blocks VSV and SARS-CoV-2 replication. These findings elucidate a previously unknown mechanism through which CD97 negatively regulates RIG-I in the antiviral innate immune response and provide a molecular basis for the development of new therapeutic strategies and the design of targeted antiviral agents.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data availability

The authors assert that all data supporting the conclusions of this study can be located in the paper and its supplementary information files or can be obtained from the corresponding author upon reasonable request.

References

  1. Shi J, Wen Z, Zhong G, Yang H, Wang C, Huang B, et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science. 2020;368:1016–20. https://doi.org/10.1126/science.abb7015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Levin AT, Hanage WP, Owusu-Boaitey N, Cochran KB, Walsh SP, Meyerowitz-Katz G. Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications. Eur J Epidemiol. 2020;35:1123–38. https://doi.org/10.1007/s10654-020-00698-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, et al. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011;472:481–5. https://doi.org/10.1038/nature09907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Li X, Hou P, Ma W, Wang X, Wang H, Yu Z, et al. SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy. Cell Mol Immunol. 2022;19:67–78. https://doi.org/10.1038/s41423-021-00807-4.

    Article  CAS  PubMed  Google Scholar 

  5. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140:805–20. https://doi.org/10.1016/j.cell.2010.01.022.

    Article  CAS  PubMed  Google Scholar 

  6. Rehwinkel J, Reis e Sousa C. RIGorous detection: exposing virus through RNA sensing. Science. 2010;327:284–286. https://doi.org/10.1126/science.1185068.

    Article  CAS  PubMed  Google Scholar 

  7. Loo Y-M, Gale M. Immune signaling by RIG-I-like receptors. Immunity. 2011;34:680–92. https://doi.org/10.1016/j.immuni.2011.05.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jiang F, Ramanathan A, Miller MT, Tang G-Q, Gale M, Patel SS, et al. Structural basis of RNA recognition and activation by innate immune receptor RIG-I. Nature. 2011;479:423–7. https://doi.org/10.1038/nature10537.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Luo D, Ding SC, Vela A, Kohlway A, Lindenbach BD, Pyle AM. Structural insights into RNA recognition by RIG-I. Cell. 2011;147:409–22. https://doi.org/10.1016/j.cell.2011.09.023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hou F, Sun L, Zheng H, Skaug B, Jiang Q-X, Chen ZJ. MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell. 2011;146:448–61. https://doi.org/10.1016/j.cell.2011.06.041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Weerawardhana A, Uddin MB, Choi J-H, Pathinayake P, Shin SH, Chathuranga K, et al. Foot-and-mouth disease virus non-structural protein 2B downregulates the RLR signaling pathway via degradation of RIG-I and MDA5. Front Immunol. 2022;13:1020262. https://doi.org/10.3389/fimmu.2022.1020262.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gack MU, Albrecht RA, Urano T, Inn K-S, Huang IC, Carnero E, et al. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe. 2009;5:439–49. https://doi.org/10.1016/j.chom.2009.04.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wallach D, Kovalenko A. Phosphorylation and dephosphorylation of the RIG-I-like receptors: a safety latch on a fateful pathway. Immunity. 2013;38:402–3. https://doi.org/10.1016/j.immuni.2013.02.014.

    Article  CAS  PubMed  Google Scholar 

  14. Wies E, Wang MK, Maharaj NP, Chen K, Zhou S, Finberg RW, et al. Dephosphorylation of the RNA sensors RIG-I and MDA5 by the phosphatase PP1 is essential for innate immune signaling. Immunity. 2013;38:437–49. https://doi.org/10.1016/j.immuni.2012.11.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hu M-M, Liao C-Y, Yang Q, Xie X-Q, Shu H-B. Innate immunity to RNA virus is regulated by temporal and reversible sumoylation of RIG-I and MDA5. J Exp Med. 2017;214:973–89. https://doi.org/10.1084/jem.20161015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Oshiumi H, Matsumoto M, Hatakeyama S, Seya T. Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote interferon-beta induction during the early phase of viral infection. J Biol Chem. 2009;284:807–17. https://doi.org/10.1074/jbc.M804259200.

    Article  CAS  PubMed  Google Scholar 

  17. Kuniyoshi K, Takeuchi O, Pandey S, Satoh T, Iwasaki H, Akira S, et al. Pivotal role of RNA-binding E3 ubiquitin ligase MEX3C in RIG-I-mediated antiviral innate immunity. Proc Natl Acad Sci USA. 2014;111:5646–51. https://doi.org/10.1073/pnas.1401674111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gao D, Yang Y-K, Wang R-P, Zhou X, Diao F-C, Li M-D, et al. REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I. PLoS ONE. 2009;4:e5760. https://doi.org/10.1371/journal.pone.0005760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Oshiumi H, Miyashita M, Inoue N, Okabe M, Matsumoto M, Seya T. The ubiquitin ligase Riplet is essential for RIG-I-dependent innate immune responses to RNA virus infection. Cell Host Microbe. 2010;8:496–509. https://doi.org/10.1016/j.chom.2010.11.008.

    Article  CAS  PubMed  Google Scholar 

  20. Gack MU, Shin YC, Joo C-H, Urano T, Liang C, Sun L, et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature. 2007;446:916–20.

    Article  CAS  PubMed  Google Scholar 

  21. Yan J, Li Q, Mao A-P, Hu M-M, Shu H-B. TRIM4 modulates type I interferon induction and cellular antiviral response by targeting RIG-I for K63-linked ubiquitination. J Mol Cell Biol. 2014;6:154–63. https://doi.org/10.1093/jmcb/mju005.

    Article  CAS  PubMed  Google Scholar 

  22. Chen W, Han C, Xie B, Hu X, Yu Q, Shi L, et al. Induction of Siglec-G by RNA viruses inhibits the innate immune response by promoting RIG-I degradation. Cell. 2013;152:467–78. https://doi.org/10.1016/j.cell.2013.01.011.

    Article  CAS  PubMed  Google Scholar 

  23. Zhao K, Zhang Q, Li X, Zhao D, Liu Y, Shen Q, et al. Cytoplasmic STAT4 promotes antiviral type I IFN production by blocking CHIP-mediated degradation of RIG-I. J Immunol. 2016;196:1209–17. https://doi.org/10.4049/jimmunol.1501224.

    Article  CAS  PubMed  Google Scholar 

  24. Wang W, Jiang M, Liu S, Zhang S, Liu W, Ma Y, et al. RNF122 suppresses antiviral type I interferon production by targeting RIG-I CARDs to mediate RIG-I degradation. Proc Natl Acad Sci USA. 2016;113:9581–6. https://doi.org/10.1073/pnas.1604277113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Arimoto K-I, Takahashi H, Hishiki T, Konishi H, Fujita T, Shimotohno K. Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proc Natl Acad Sci USA. 2007;104:7500–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Yang W, Ru Y, Ren J, Bai J, Wei J, Fu S, et al. G3BP1 inhibits RNA virus replication by positively regulating RIG-I-mediated cellular antiviral response. Cell Death Dis. 2019;10:946. https://doi.org/10.1038/s41419-019-2178-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Shen Y, Tang K, Chen D, Hong M, Sun F, Wang S, et al. Riok3 inhibits the antiviral immune response by facilitating TRIM40-mediated RIG-I and MDA5 degradation. Cell Rep. 2021;35:109272. https://doi.org/10.1016/j.celrep.2021.109272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Yona S, Lin H-H, Siu WO, Gordon S, Stacey M. Adhesion-GPCRs: emerging roles for novel receptors. Trends Biochem Sci. 2008;33:491–500. https://doi.org/10.1016/j.tibs.2008.07.005.

    Article  CAS  PubMed  Google Scholar 

  29. Hsiao C-C, Wang W-C, Kuo W-L, Chen H-Y, Chen T-C, Hamann J, et al. CD97 inhibits cell migration in human fibrosarcoma cells by modulating TIMP-2/MT1- MMP/MMP-2 activity-role of GPS autoproteolysis and functional cooperation between the N- and C-terminal fragments. FEBS J. 2014;281:4878–91. https://doi.org/10.1111/febs.13027.

    Article  CAS  PubMed  Google Scholar 

  30. Hamann J, Stortelers C, Kiss-Toth E, Vogel B, Eichler W, van Lier RA. Characterization of the CD55 (DAF)-binding site on the seven-span transmembrane receptor CD97. Eur J Immunol. 1998;28:1701–7

    Article  CAS  PubMed  Google Scholar 

  31. Kwakkenbos MJ, Pouwels W, Matmati M, Stacey M, Lin H-H, Gordon S, et al. Expression of the largest CD97 and EMR2 isoforms on leukocytes facilitates a specific interaction with chondroitin sulfate on B cells. J Leukoc Biol. 2005;77:112–9

    Article  CAS  PubMed  Google Scholar 

  32. Wandel E, Saalbach A, Sittig D, Gebhardt C, Aust G. Thy-1 (CD90) is an interacting partner for CD97 on activated endothelial cells. J Immunol. 2012;188:1442–50. https://doi.org/10.4049/jimmunol.1003944.

    Article  CAS  PubMed  Google Scholar 

  33. Wang T, Ward Y, Tian L, Lake R, Guedez L, Stetler-Stevenson WG, et al. CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counterreceptors on endothelial cells. Blood. 2005;105:2836–44.

    Article  CAS  PubMed  Google Scholar 

  34. Jaspars LH, Vos W, Aust G, Van Lier RA, Hamann J. Tissue distribution of the human CD97 EGF-TM7 receptor. Tissue Antigens. 2001;57:325–31.

    Article  CAS  PubMed  Google Scholar 

  35. Liu D, Duan L, Rodda LB, Lu E, Xu Y, An J, et al. CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells. Science. 2022;375:eabi5965. https://doi.org/10.1126/science.abi5965.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Cerny O, Godlee C, Tocci R, Cross NE, Shi H, Williamson JC, et al. CD97 stabilises the immunological synapse between dendritic cells and T cells and is targeted for degradation by the Salmonella effector SteD. PLoS Pathog. 2021;17:e1009771. https://doi.org/10.1371/journal.ppat.1009771.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Veninga H, Becker S, Hoek RM, Wobus M, Wandel E, van der Kaa J, et al. Analysis of CD97 expression and manipulation: antibody treatment but not gene targeting curtails granulocyte migration. J Immunol. 2008;181:6574–83

    Article  CAS  PubMed  Google Scholar 

  38. Hou J, Han L, Zhao Z, Liu H, Zhang L, Ma C, et al. USP18 positively regulates innate antiviral immunity by promoting K63-linked polyubiquitination of MAVS. Nat Commun. 2021;12:2970. https://doi.org/10.1038/s41467-021-23219-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wang S, Hou P, Pan W, He W, He D C, Wang H, et al. DDIT3 targets Innate Immunity via the DDIT3-OTUD1-MAVS pathway to promote bovine viral diarrhea virus replication. J Virol. 2021;95. https://doi.org/10.1128/JVI.02351-20.

  40. Hou P, Zhao M, He W, He H, Wang H. Cellular microRNA bta-miR-2361 inhibits bovine herpesvirus 1 replication by directly targeting EGR1 gene. Vet Microbiol. 2019;233:174–83. https://doi.org/10.1016/j.vetmic.2019.05.004.

    Article  CAS  PubMed  Google Scholar 

  41. Hou P, Wang X, Wang H, Wang T, Yu Z, Xu C, et al. The ORF7a protein of SARS-CoV-2 initiates autophagy and limits autophagosome-lysosome fusion via degradation of SNAP29 to promote virus replication. Autophagy. 2022. https://doi.org/10.1080/15548627.2022.2084686.

  42. Wang X, Zhao Y, Yan F, Wang T, Sun W, Feng N, et al. Viral and host transcriptomes in SARS-CoV-2-infected human lung cells. J Virol. 2021;95:e0060021. https://doi.org/10.1128/JVI.00600-21.

    Article  PubMed  Google Scholar 

  43. Yin Y, Xu X, Tang J, Zhang W, Zhangyuan G, Ji J, et al. CD97 promotes tumor aggressiveness through the traditional G protein-coupled receptor-mediated signaling in hepatocellular carcinoma. Hepatology. 2018;68:1865–78. https://doi.org/10.1002/hep.30068.

    Article  CAS  PubMed  Google Scholar 

  44. Wang J, Yang G, Wang X, Wen Z, Shuai L, Luo J, et al. SARS-CoV-2 uses metabotropic glutamate receptor subtype 2 as an internalization factor to infect cells. Cell Discov. 2021;7:119. https://doi.org/10.1038/s41421-021-00357-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Zheng N, Shabek N. Ubiquitin ligases: structure, function, and regulation. Annu Rev Biochem. 2017;86:129–57. https://doi.org/10.1146/annurev-biochem-060815-014922.

    Article  CAS  PubMed  Google Scholar 

  46. Yang L-Y, Liu X-F, Yang Y, Yang L-L, Liu K-W, Tang Y-B, et al. Biochemical features of the adhesion G protein-coupled receptor CD97 related to its auto-proteolysis and HeLa cell attachment activities. Acta Pharmacol Sin. 2017;38:56–68. https://doi.org/10.1038/aps.2016.89.

    Article  CAS  PubMed  Google Scholar 

  47. Ma C, Lv Q, Teng S, Yu Y, Niu K, Yi C. Identifying key genes in rheumatoid arthritis by weighted gene co-expression network analysis. Int J Rheum Dis. 2017;20:971–9. https://doi.org/10.1111/1756-185X.13063.

    Article  CAS  PubMed  Google Scholar 

  48. Ward Y, Lake R, Martin PL, Killian K, Salerno P, Wang T, et al. CD97 amplifies LPA receptor signaling and promotes thyroid cancer progression in a mouse model. Oncogene. 2013;32:2726–38. https://doi.org/10.1038/onc.2012.301.

    Article  CAS  PubMed  Google Scholar 

  49. Li C, Liu D-R, Li G-G, Wang H-H, Li X-W, Zhang W, et al. CD97 promotes gastric cancer cell proliferation and invasion through exosome-mediated MAPK signaling pathway. World J Gastroenterol. 2015;21:6215–28. https://doi.org/10.3748/wjg.v21.i20.6215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Liu D, Li C, Trojanowicz B, Li X, Shi D, Zhan C, et al. CD97 promotion of gastric carcinoma lymphatic metastasis is exosome dependent. Gastric Cancer. 2016;19:754–66. https://doi.org/10.1007/s10120-015-0523-y.

    Article  CAS  PubMed  Google Scholar 

  51. Ward Y, Lake R, Yin JJ, Heger CD, Raffeld M, Goldsmith PK, et al. LPA receptor heterodimerizes with CD97 to amplify LPA-initiated RHO-dependent signaling and invasion in prostate cancer cells. Cancer Res. 2011;71:7301–11. https://doi.org/10.1158/0008-5472.CAN-11-2381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Huang H, Xiong Q, Wang N, Chen R, Ren H, Siwko S, et al. Kisspeptin/GPR54 signaling restricts antiviral innate immune response through regulating calcineurin phosphatase activity. Sci Adv. 2018;4:eaas9784. https://doi.org/10.1126/sciadv.aas9784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Xiong Q, Huang H, Wang N, Chen R, Chen N, Han H, et al. Metabolite-sensing G protein coupled receptor TGR5 protects host from viral infection through amplifying type I interferon responses. Front Immunol. 2018;9:2289. https://doi.org/10.3389/fimmu.2018.02289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, et al. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science. 2015;347:aaa2630. https://doi.org/10.1126/science.aaa2630.

    Article  CAS  PubMed  Google Scholar 

  55. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol. 2004;5:730–7.

    Article  CAS  PubMed  Google Scholar 

  56. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature. 2006;441:101–5.

    Article  CAS  PubMed  Google Scholar 

  57. Kato H, Sato S, Yoneyama M, Yamamoto M, Uematsu S, Matsui K, et al. Cell type-specific involvement of RIG-I in antiviral response. Immunity. 2005;23:19–28.

    Article  CAS  PubMed  Google Scholar 

  58. Chen S-T, Chen L, Lin D S-C, Chen S-Y, Tsao Y-P, Guo H, et al. NLRP12 regulates anti-viral RIG-I activation via interaction with TRIM25. Cell Host Microbe. 2019;25. https://doi.org/10.1016/j.chom.2019.02.013.

  59. Hao Q, Jiao S, Shi Z, Li C, Meng X, Zhang Z, et al. A non-canonical role of the p97 complex in RIG-I antiviral signaling. EMBO J. 2015;34:2903–20. https://doi.org/10.15252/embj.201591888.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Liu W, Li J, Zheng W, Shang Y, Zhao Z, Wang S, et al. Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses. ELife. 2017;6. https://doi.org/10.7554/eLife.24425.

  61. Park GB, Kim D. MicroRNA-503-5p inhibits the CD97-mediated JAK2/STAT3 pathway in metastatic or paclitaxel-resistant ovarian cancer cells. Neoplasia. 2019;21:206–15. https://doi.org/10.1016/j.neo.2018.12.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Planas D, Bruel T, Staropoli I, Guivel-Benhassine F, Porrot F, Maes P, et al. Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies. Nat Commun. 2023;14:824. https://doi.org/10.1038/s41467-023-36561-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Foo CS, Abdelnabi R, Vangeel L, De Jonghe S, Jochmans D, Weynand B, et al. Ivermectin does not protect against SARS-CoV-2 infection in the Syrian hamster model. Microorganisms. 2022;10. https://doi.org/10.3390/microorganisms10030633.

  64. Shi G, Kenney AD, Kudryashova E, Zani A, Zhang L, Lai KK, et al. Opposing activities of IFITM proteins in SARS-CoV-2 infection. EMBO J. 2021;40:e106501. https://doi.org/10.15252/embj.2020106501.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The study was partially supported by grants from the National Natural Science Fund of China (32072834, 31972665), Special fund support for Taishan Scholar Project (H. H, tspd20181207), Shandong Provincial Natural Science Foundation, China (ZR2021MC050), and Jinan Innovation Team (202228060).

Author information

Author notes

  1. These authors contributed equally: Huasong Chang, Peili Hou, Xuefeng Wang.

Authors and Affiliations

  1. Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan, Shandong, 250014, China

    Huasong Chang, Peili Hou, Aibiao Xiang, Hao Wu, Wenjing Qi, Rukun Yang, Xue Wang, Xingyu Li, Guimin Zhao, Hongmei Wang & Hongbin He

  2. Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Taian, Shandong, 271018, China

    Peili Hou & Hongbin He

  3. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin, 130122, China

    Xuefeng Wang, Weiyang Sun, Tiecheng Wang & Yuwei Gao

  4. Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, China

    Wenqi He

  5. The College of Arts and Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Daniel Chang He

Authors
  1. Huasong Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peili Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xuefeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aibiao Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenjing Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rukun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xue Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xingyu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wenqi He
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Guimin Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Weiyang Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tiecheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Daniel Chang He
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Hongmei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yuwei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Hongbin He
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HBH, YWG, and HMW conceptualized the study; HBH, HSC, and PLH designed the experiments; XFW performed SARS-CoV-2 infection in vitro and in vivo experiments; HSC, ABX, and HW performed VSV infection in vivo and pathological experiments; WQH directed animal experiments; HSC, WJQ, RKY, XW, and DCH performed most of the immunoblotting, immunofluorescence, and qPCR experiments; XYL and GMZ designed and constructed the recombinant plasmids of CD97; HSC, PLH, and XFW collected and analyzed the data; WYS and TCW participated in discussions; HSC wrote the original draft; HBH and PLH edited and revised the original draft. All the authors reviewed and approved the final manuscript.

Corresponding authors

Correspondence to Hongmei Wang, Yuwei Gao or Hongbin He.

Ethics declarations

Competing interests

The authors declare no competing interests.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chang, H., Hou, P., Wang, X. et al. CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation. Cell Mol Immunol 20, 1457–1471 (2023). https://doi.org/10.1038/s41423-023-01103-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41423-023-01103-z

Keywords

Search

Advanced search

Quick links