机构：[1]Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China中山大学附属第三医院[2]Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China中山大学附属第三医院[3]Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China[4]Department of Traditional Chinese Medicine, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China中山大学附属第三医院
We have previously observed the downregulation of TMEM2 in the liver tissue of patients with chronic hepatitis B virus (HBV) infection and in HepG2.2.15 cells with HBV genomic DNA. In the present study, we investigated the role and mechanism of TMEM2 in HepG2 and HepG2.2.15 during HBV infection HepG2 and HepG2.2.15. HepG2 shTMEM2 cells with stable TMEM2 knockdown and HepG2 TMEM2 and HepG2.2.15 TMEM2 cells with stable TMEM2 overexpression were established using lentivirus vectors. We observed reduced expression of TMEM2 in HBV-infected liver tissues and HepG2.2.15 cells. HBsAg, HBcAg, HBV DNA, and HBV cccDNA levels were significantly increased in HepG2 shTMEM2 cells but decreased in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells compared with naive HepG2 cells. On the basis of the western blotting results, the JAK-STAT signaling pathway was inhibited in HepG2 shTMEM2 cells but activated in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells. In addition, reduced and increased expression of the antiviral proteins MxA and OAS1 was observed in TMEM2-silenced cells (HepG2 shTMEM2 cells) and TMEM2-overexpressing cells (HepG2 TMEM2 and HepG2.2.15 TMEM2 cells), respectively. The expression of Interferon regulatory factor 9 (IRF9) was not affected by TMEM2. However, we found that overexpression and knockdown of TMEM2, respectively, promoted and inhibited importation of IRF9 into nuclei. The luciferase reporter assay showed that IRF9 nuclear translocation affected interferon-stimulated response element activities. In addition, the inhibitory effects of TMEM2 on HBV infection in HepG2 shTMEM2 cells was significantly enhanced by pre-treatment with interferon but significantly inhibited in HepG2.2.15 TMEM2 cells by pre-treatment with JAK1 inhibitor. TMEM2 inhibits HBV infection in HepG2 and HepG2.2.15 by activating the JAK-STAT signaling pathway.
基金：
National Science and
Technology Major Project (2016ZX10002010, 2016ZX10002009, and 2016ZX10002008),
the National Natural Science Foundation of China (81370535, 81570539, and 81202319),
Basic Research Funds of the Key Universities (12ykpy35 and 13ykzd17), the Natural
Science Foundation of Guangdong Province (S2013010016014, 2014A030313089), the
Guangzhou Science and Technology Project (1561000155), and the 111 Project (grant no.
B12003). We thank Prof. Yiming Wang and Dr. Qiang Zhao for helpful discussion.
第一作者机构：[1]Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China[2]Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China[3]Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China[2]Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China[3]Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China[*1]Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China
推荐引用方式(GB/T 7714)：
Zhu X,Xie C,Li Y-M,et al.TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK-STAT signaling pathway.[J].CELL DEATH & DISEASE.2016,7:doi:10.1038/cddis.2016.146.
APA：
Zhu X,Xie C,Li Y-M,Huang Z-L,Zhao Q-Y...&Peng L.(2016).TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK-STAT signaling pathway..CELL DEATH & DISEASE,7,
MLA：
Zhu X,et al."TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK-STAT signaling pathway.".CELL DEATH & DISEASE 7.(2016)
生物学