Expression of Interferon Effector Gene SART1 Correlates with Interferon Treatment Response against Hepatitis B Infection
Interferon-α (IFN-α) has limited response rate in the treatment of chronic hepatitis B (CHB). The underlying mechanism of differential responsiveness to IFN remains elusive. It has been recently reported that SART1 mediates antiviral effects of IFN-α in the hepatitis C virus (HCV) cell culture model...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/3894816 |
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| author | Yong Li Chuanlong Zhu Faxi Wang Tiantian Zhu Jun Li Shufeng Liu Fei Xiao |
| author_facet | Yong Li Chuanlong Zhu Faxi Wang Tiantian Zhu Jun Li Shufeng Liu Fei Xiao |
| author_sort | Yong Li |
| collection | DOAJ |
| description | Interferon-α (IFN-α) has limited response rate in the treatment of chronic hepatitis B (CHB). The underlying mechanism of differential responsiveness to IFN remains elusive. It has been recently reported that SART1 mediates antiviral effects of IFN-α in the hepatitis C virus (HCV) cell culture model. In this study, we investigated the role of SART1 in antiviral activity of IFN-α against hepatitis B virus (HBV) using blood and liver biopsy samples from chronic hepatitis B patients treated with pegylated IFN-α and HepG2 cells transfected with cloned HBV DNA. We observed that the basal SART1 expression in liver and PBMCs before IFN treatment was significantly higher in responders than in nonresponders. Furthermore, baseline SART1 expression level positively correlated with the degree of HBV DNA and HBeAg decline after IFN treatment. Mechanistically, silencing SART1 abrogated the antiviral activity of IFN-α, reduced the expression of IFN-stimulated genes (ISGs) Mx, OAS, and PKR, and attenuated JAK-STAT signaling in HepG2 cells, suggesting that SART1 regulates IFN-mediated antiviral activity through JAK-STAT signaling and ISG expression. Our study elucidates the important role of SART1 in IFN-mediated anti-HBV response and provides new insights into understanding variation of IFN treatment response in CHB patients. |
| format | Article |
| id | doaj-art-dc240f136d044feb898adfeba97d90dc |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-dc240f136d044feb898adfeba97d90dc2025-02-03T01:30:15ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/38948163894816Expression of Interferon Effector Gene SART1 Correlates with Interferon Treatment Response against Hepatitis B InfectionYong Li0Chuanlong Zhu1Faxi Wang2Tiantian Zhu3Jun Li4Shufeng Liu5Fei Xiao6Department and Institute of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaThe Center for Biomedical Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaCenter for Immunology and Infectious Diseases, Biosciences Division, SRI International, Harrisonburg, VA 22802, USADepartment of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAInterferon-α (IFN-α) has limited response rate in the treatment of chronic hepatitis B (CHB). The underlying mechanism of differential responsiveness to IFN remains elusive. It has been recently reported that SART1 mediates antiviral effects of IFN-α in the hepatitis C virus (HCV) cell culture model. In this study, we investigated the role of SART1 in antiviral activity of IFN-α against hepatitis B virus (HBV) using blood and liver biopsy samples from chronic hepatitis B patients treated with pegylated IFN-α and HepG2 cells transfected with cloned HBV DNA. We observed that the basal SART1 expression in liver and PBMCs before IFN treatment was significantly higher in responders than in nonresponders. Furthermore, baseline SART1 expression level positively correlated with the degree of HBV DNA and HBeAg decline after IFN treatment. Mechanistically, silencing SART1 abrogated the antiviral activity of IFN-α, reduced the expression of IFN-stimulated genes (ISGs) Mx, OAS, and PKR, and attenuated JAK-STAT signaling in HepG2 cells, suggesting that SART1 regulates IFN-mediated antiviral activity through JAK-STAT signaling and ISG expression. Our study elucidates the important role of SART1 in IFN-mediated anti-HBV response and provides new insights into understanding variation of IFN treatment response in CHB patients.http://dx.doi.org/10.1155/2016/3894816 |
| spellingShingle | Yong Li Chuanlong Zhu Faxi Wang Tiantian Zhu Jun Li Shufeng Liu Fei Xiao Expression of Interferon Effector Gene SART1 Correlates with Interferon Treatment Response against Hepatitis B Infection Mediators of Inflammation |
| title | Expression of Interferon Effector Gene SART1 Correlates with Interferon Treatment Response against Hepatitis B Infection |
| title_full | Expression of Interferon Effector Gene SART1 Correlates with Interferon Treatment Response against Hepatitis B Infection |
| title_fullStr | Expression of Interferon Effector Gene SART1 Correlates with Interferon Treatment Response against Hepatitis B Infection |
| title_full_unstemmed | Expression of Interferon Effector Gene SART1 Correlates with Interferon Treatment Response against Hepatitis B Infection |
| title_short | Expression of Interferon Effector Gene SART1 Correlates with Interferon Treatment Response against Hepatitis B Infection |
| title_sort | expression of interferon effector gene sart1 correlates with interferon treatment response against hepatitis b infection |
| url | http://dx.doi.org/10.1155/2016/3894816 |
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