title: TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK-STAT signaling pathway.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China.|Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China.|Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: C
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Traditional Chinese Medicine, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China.
authors.forename: Y-M
authors.initials: YM
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China.|Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Z-L
authors.initials: ZL
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China.|Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Q-Y
authors.initials: QY
authors.lastname: Zhao
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China.|Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Z-X
authors.initials: ZX
authors.lastname: Hu
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China.|Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: P-P
authors.initials: PP
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China.|Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Y-R
authors.initials: YR
authors.lastname: Gu
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China.|Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Z-L
authors.initials: ZL
authors.lastname: Gao
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong Province, China.|Guangdong Provincial Key Laboratory of Liver Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: L
authors.initials: L
authors.lastname: Peng
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects; D056945:Hep G2 Cells; D018963:Hepatitis Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000378:metabolism; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D064547:Myxovirus Resistance Proteins / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C408224:CEMIP2 protein, human; D004279:DNA, Viral; D018963:Hepatitis Antigens; C494227:IRF9 protein, human; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; C579071:MX1 protein, human; D008565:Membrane Proteins; D064547:Myxovirus Resistance Proteins; D047428:Protein Kinase Inhibitors; D050791:STAT Transcription Factors; D053612:Janus Kinases; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase