CK1α upregulates the IFNAR1 expression to prompt the anti-HBV effect of type I IFN in hepatoma carcinoma cells

Jing Xiong; Yanjun Jiang; Jinru Zhang; Yanmeng Chen; Yuan Hu

doi:10.1016/j.virs.2022.08.004

December 2022

Citation: Jing Xiong, Yanjun Jiang, Jinru Zhang, Yanmeng Chen, Yuan Hu. CK1α upregulates the IFNAR1 expression to prompt the anti-HBV effect of type I IFN in hepatoma carcinoma cells .VIROLOGICA SINICA, 2022, 37(6) : 894-903. http://dx.doi.org/10.1016/j.virs.2022.08.004

CK1α upregulates the IFNAR1 expression to prompt the anti-HBV effect of type I IFN in hepatoma carcinoma cells

Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China

Corresponding author: Yuan Hu, huyuan@cqmu.edu.cn
Received Date: 27 January 2022
Accepted Date: 08 August 2022
Available online: 17 August 2022

Abstract

Casein kinase 1α (CK1α) mediates the phosphorylation and degradation of interferon-α/β receptor 1 (IFNAR1) in response to viral infection. However, how CK1α regulates hepatitis B virus (HBV) replication and the anti-HBV effects of IFN-α are less reported. Here we show that CK1α can interact with IFNAR1 in hepatoma carcinoma cells and increased the abundance of IFNAR1 by reducing the ubiquitination levels in the presence of HBV. Furthermore, CK1α promotes the IFN-α triggered JAK-STAT signaling pathway and consequently enhances the antiviral effects of IFN-α against HBV replication. Our results collectively provide evidence that CK1α positively regulates the anti-HBV activity of IFN-α in hepatoma carcinoma cells, which would be a promising therapeutic target to improve the effectiveness of IFN-α therapy to cure CHB.
- Hepatitis B virus (HBV)
- , Casein kinase 1α (CK1α)
- , Interferon-α/β receptor 1 (IFNAR1)
- , Interferon-α (IFN-α)

Electronic Supplementary Material

10.1016j.virs.2022.08.004-ESM.zip
References
1. Brubaker, S.W.B., Zanoni, K.S., Kagan, I., J. C., 2015. Innate immune pattern recognition:a cell biological perspective. Annu. Rev. Immunol. 33, 257–290.
2. Buster, E.H., Flink, H.J., Cakaloglu, Y., Simon, K., Trojan, J., Tabak, F., So, T.M., Feinman, S.V., Mach, T., Akarca, U.S., Schutten, M., Tielemans, W., Van Vuuren, A.J., Hansen, B.E., Janssen, H.L., 2008. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b.Gastroenterology 135, 459–467.
3. Chen, Y., Hu, J., Cai, X., Huang, Y., Zhou, X., Tu, Z., Hu, J., Tavis, J.E., Tang, N., Huang, A., Hu, Y., 2018. APOBEC3B edits HBV DNA and inhibits HBV replication during reverse transcription. Antivir. Res. 149, 16–25.
4. Chen, Y., Shen, B., Zheng, X., Long, Q., Xia, J., Huang, Y., Cai, X., Wang, D., Chen, J., Tang, N., Huang, A., Hu, Y., 2020. DHX9 interacts with APOBEC3B and attenuates the anti-HBV effect of APOBEC3B. Emerg. Microb. Infect. 9, 366–377.
5. Cheng, X.,X.Y., Serti, E., Block, Pd, Chung, M., Chayama, K., Rehermann, B., Liang, Tj, 2017. Hepatitis B virus evades innate immunity of hepatocytes but activates cytokine production by macrophages. Hepatology 66, 1779–1793.
6. Fuchs, S.Y., 2013. Hope and fear for interferon: the receptor-centric outlook on the future of interferon therapy. J. Interferon Cytokine Res. 33, 211–225.
7. Janahi, E.M., McGarvey, M.J., 2013. The inhibition of hepatitis B virus by APOBEC cytidine deaminases. J. Viral Hepat. 20, 821–828.
8. Jiang, S., Zhang, M., Sun, J., Yang, X., 2018. Casein kinase 1α: biological mechanisms and theranostic potential. Cell Commun. Signal. 16, 23.
9. Konerman, M.A., Lok, A.S., 2016. Interferon treatment for hepatitis B. Clin. Liver Dis. 20, 645–665.
10. Kumar, K.G., Krolewski, J.J., Fuchs, S.Y., 2004. Phosphorylation and specific ubiquitin acceptor sites are required for ubiquitination and degradation of the IFNAR1 subunit of type I interferon receptor. J. Biol. Chem. 279, 46614–46620.
11. Kumar, K.G., Tang, W., Ravindranath, A.K., Clark, W.A., Croze, E., Fuchs, S.Y., 2003. SCF(HOS) ubiquitin ligase mediates the ligand-induced down-regulation of the interferon-alpha receptor. EMBO J. 22, 5480–5490.
12. Lauterbach-Rivière, L., Bergez, M., Mönch, S., Qu, B., Riess, M., Vondran, F.W.R., Liese, J., Hornung, V., Urban, S., König, R., 2020. Hepatitis B virus DNA is a substrate for the cGAS/STING pathway but is not sensed in infected hepatocytes. Viruses 12, 592.
13. Liu, J., Carvalho, L.P., Bhattacharya, S., Carbone, C.J., Kumar, K.G., Leu, N.A., Yau, P.M., Donald, R.G., Weiss, M.J., Baker, D.P., Mclaughlin, K.J., Scott, P., Fuchs, S.Y., 2009.Mammalian casein kinase 1alpha and its leishmanial ortholog regulate stability of IFNAR1 and type I interferon signaling. Mol. Cell Biol. 29, 6401–6412.
14. Lu, H.L.L.,F., 2013. Melanoma differentiation-associated gene 5 senses hepatitis B virus and activates innate immune signaling to suppress virus replication. J. Immunol. 191, 3264–3276.
15. Nguyen, M.H., Wong, G., Gane, E., Kao, J.H., Dusheiko, G., 2020. Hepatitis B virus:advances in prevention, diagnosis, and therapy. Clin. Microbiol. Rev. 33, e00046, 00019.
16. Pietro Lampertico, K.A., Berg, Thomas, Buti, Maria, Janssen, Harry L a, George, Papatheodoridis, Zoulim, Fabien, Frank, Tacke, 2017. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J. Hepatol. 67, 370–398.
17. Poh, Z., Goh, B.B., Chang, P.E., Tan, C.K., 2015. Rates of cirrhosis and hepatocellular carcinoma in chronic hepatitis B and the role of surveillance: a 10-year follow-up of 673 patients. Eur. J. Gastroenterol. Hepatol. 27, 638–643.
18. Roers, A., Hiller, B., Hornung, V., 2016. Recognition of endogenous nucleic acids by the innate immune system. Immunity 44, 739–754.
19. Sato, S., Li, K., Kameyama, T., Hayashi, T., Ishida, Y., Murakami, S., Watanabe, T., Iijima, S., Sakurai, Y., Watashi, K., Tsutsumi, S., Sato, Y., Akita, H., Wakita, T., Rice, C.M., Harashima, H., Kohara, M., Tanaka, Y., Takaoka, A., 2015. The RNA sensor RIG-I dually functions as an innate sensor and direct antiviral factor for hepatitis B virus. Immunity 42, 123–132.
20. Schreiber, G., 2017. The molecular basis for differential type I interferon signaling. J. Biol. Chem. 292, 7285–7294.
21. Sommer, A.F., Rivière, L., Qu, B., Schott, K., Riess, M., Ni, Y., Shepard, C., Schnellbächer, E., Finkernagel, M., Himmelsbach, K., Welzel, K., Kettern, N., Donnerhak, C., Münk, C., Flory, E., Liese, J., Kim, B., Urban, S., König, R., 2016. Restrictive influence of SAMHD1 on Hepatitis B Virus life cycle. Sci. Rep. 6, 26616.
22. Terrault, N.A., Lok, A.S.F., Mcmahon, B.J., Chang, K.M., Hwang, J.P., Jonas, M.M., Brown Jr., R.S., Bzowej, N.H., Wong, J.B., 2018. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 67, 1560–1599.
23. Van Zonneveld, M., Honkoop, P., Hansen, B.E., Niesters, H.G., Darwish Murad, S., De Man, R.A., Schalm, S.W., Janssen, H.L., 2004. Long-term follow-up of alphainterferon treatment of patients with chronic hepatitis B. Hepatology 39, 804–810.
24. Wang, Y.X., Niklasch, M., Liu, T., Wang, Y., Shi, B., Yuan, W., Baumert, T.F., Yuan, Z., Tong, S., Nassal, M., Wen, Y.M., 2020. Interferon-inducible MX2 is a host restriction factor of hepatitis B virus replication. J. Hepatol. 72, 865–876.
25. Xia, C., Wolf, J.J., Vijayan, M., Studstill, C.J., Ma, W., Hahm, B., 2018. Casein kinase 1α mediates the degradation of receptors for type I and type II interferons caused by hemagglutinin of influenza A virus. J. Virol. 92, e00006–18.
26. Xia, C.A., Hahm, B., P., 2018. Viral dedication to vigorous destruction of interferon receptors. Virology 522, 19–26.
27. Zhao, H., Kurbanov, F., Wan, M.B., Yin, Y.K., Niu, J.Q., Hou, J.L., Wei, L., Wang, G.Q., Tanaka, Y., Mizokami, M., Si, C.W., 2007. Genotype B and younger patient age associated with better response to low-dose therapy: a trial with pegylated/ nonpegylated interferon-alpha-2b for hepatitis B e antigen-positive patients with chronic hepatitis B in China. Clin. Infect. Dis. 44, 541–548.
28. Zheng, H., Qian, J., Varghese, B., Baker, D.P., Fuchs, S., 2011. Ligand-stimulated downregulation of the alpha interferon receptor: role of protein kinase D2. Mol. Cell Biol. 31, 710–720.
Proportional views