TMEM2 binds to CSNK2A3 to inhibit HBV infection via activation of the JAK/STAT pathway

• DOI: 10.1016/j.yexcr.2021.112517
• Publication Date: 2021-02-15T05:11:50Z
• Authors: Hu Zhou; Xiuhua Jia; Kunpeng Hu; Zhishuo Mo; Wenxiong Xu; Liang Peng; Ke Wang; Xiang Zhu
• Keywords: Hepatitis B virus; 0303 health sciences; Carcinoma, Hepatocellular; Liver Neoplasms; Brain; Membrane Proteins; Janus Kinase 1; Hepatitis B; 3. Good health; PPAR gamma; STAT Transcription Factors; 03 medical and health sciences; Epilepsy, Temporal Lobe; Case-Control Studies; Tumor Cells, Cultured; Humans; Casein Kinase II

To investigate mechanisms that TMEM2 activation inhibits hepatitis B virus (HBV) infection in hepatocarcinoma (HCC) cells, co-immunoprecipitation (Co-IP) and mass spectrometry were used in screening interacting proteins for TMEM2. Levels of casein kinase 2 subunit α3 (CSNK2A3) in HCC cells were found to be inhibited or overexpressed using siRNAs and pcDNA3.1-CSNK2A3, respectively. Effect of CSNK2A3 expression on cell proliferation was analyzed using MTS, while its effect on HBV infection was measured using ddPCR and IHC. Western blotting and JAK inhibitor ruxolitinib were also used to determine whether TMEM2-regulated CSNK2A3 expression and HBV infection were affected by JAK-STAT signaling. Co-IP and mass spectrometry results showed that CSNK2A3 interacts with TMEM2. Moreover, overexpression of CSNK2A3 significantly inhibited cell proliferation, while inhibition of CSNK2A3 promoted proliferation of HCC cells. In addition, overexpression of CSNK2A3 was observed to significantly enhance HBV infection, while siRNA knockdown of CSNK2A3 inhibited HBV infection. Notably, effect of CSNK2A3 overexpression on HBV infection was suppressed by TMEM2 overexpression. Further mechanistic analyses have revealed that TMEM2 could antagonize the effects of CSNK2A3 on cell proliferation and HBV infection via JAK-STAT pathway activation. In conclusion, TMEM2 has been determined to bind to CSNK2A3 to inhibit HBV infection via activation of the JAK-STAT pathway.