IP-10 Interferes With the Antiviral Response of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection
BackgroundIncreased interferon (IFN)-gamma inducible protein-10 (IP-10) level has been shown to be associated with sustained virologic responses (SVRs) to pegylated interferon-alpha 2a/ribavirin-based therapy in patients with chronic hepatitis C (CHC). We investigated the relationship between IP-10...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-07-01
|
| Series: | Frontiers in Public Health |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fpubh.2022.911551/full |
| _version_ | 1818195810067677184 |
|---|---|
| author | Yadong Wang Yangyang Hu Xing Zhang Yue Luo Luyuan Ma Jingjing Lu Qianfei Liang Chengjun Xu Caiyan Zhao Calvin Q. Pan Calvin Q. Pan |
| author_facet | Yadong Wang Yangyang Hu Xing Zhang Yue Luo Luyuan Ma Jingjing Lu Qianfei Liang Chengjun Xu Caiyan Zhao Calvin Q. Pan Calvin Q. Pan |
| author_sort | Yadong Wang |
| collection | DOAJ |
| description | BackgroundIncreased interferon (IFN)-gamma inducible protein-10 (IP-10) level has been shown to be associated with sustained virologic responses (SVRs) to pegylated interferon-alpha 2a/ribavirin-based therapy in patients with chronic hepatitis C (CHC). We investigated the relationship between IP-10 and treatment response in patients with CHC treated with direct-acting antiviral agents (DAAs) therapy.MethodsWe measured the dynamic changes of IP-10 in samples from 90 patients with CHC. The serum IP-10 levels, intrahepatic expressions of IP-10 mRNA, and protein were determined, respectively. For the in vitro experiments, the expression changes of IP-10 in hepatitis C virus (HCV)-replicating Huh-7 cells with or without non-structural protein 5A (NS5A) inhibitor were analyzed using real-time reverse transcription-polymerase chain reaction and Western blotting.ResultsPatients with chronic hepatitis C had increased baseline IP-10 levels, intrahepatic IP-10 mRNA, and protein expression. After initiating DAAs therapy, serum IP-10 levels decreased gradually in patients who achieved cure, whereas in patients who failed the therapy, IP-10 levels did not change significantly or recovered from the initial decline. Multivariate logistic regression analysis confirmed that baseline IP-10 level ≤ 450 pg/ml and decline >30% at 12 weeks independently predicted the SVR in patients with CHC who received DAAs. In vitro, the expression of IP-10 mRNA and protein in HCV-replicating Huh-7 cells increased significantly. However, such activities were downregulated by NS5A inhibitor, followed by the reduction of HCV RNA levels and a decline in IP-10 levels.ConclusionIP-10 interfered with HCV replication in hepatocytes and the dynamic decline in IP-10 levels during DAA treatment predicted the SVR in patients with CHC. |
| first_indexed | 2024-12-12T01:24:06Z |
| format | Article |
| id | doaj.art-d2b510c64f46473da07eee5981b5fed4 |
| institution | Directory Open Access Journal |
| issn | 2296-2565 |
| language | English |
| last_indexed | 2024-12-12T01:24:06Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Public Health |
| spelling | doaj.art-d2b510c64f46473da07eee5981b5fed42022-12-22T00:43:09ZengFrontiers Media S.A.Frontiers in Public Health2296-25652022-07-011010.3389/fpubh.2022.911551911551IP-10 Interferes With the Antiviral Response of Direct-Acting Antiviral Agents for Hepatitis C Virus InfectionYadong Wang0Yangyang Hu1Xing Zhang2Yue Luo3Luyuan Ma4Jingjing Lu5Qianfei Liang6Chengjun Xu7Caiyan Zhao8Calvin Q. Pan9Calvin Q. Pan10Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Infectious Diseases, The Affiliated Hospital of Chengde Medical University, Chengde, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Infectious Diseases, People's Hospital of Kuancheng Manchu Nationality Autonomous County, Chengde, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, ChinaCenter for Liver Diseases, Beijing Ditan Hospital, Capital Medical Univerisity, Beijing, ChinaDivision of Gastroenterology and Hepatology, NYU Langone Health, New York University School of Medicine, New York, NY, United StatesBackgroundIncreased interferon (IFN)-gamma inducible protein-10 (IP-10) level has been shown to be associated with sustained virologic responses (SVRs) to pegylated interferon-alpha 2a/ribavirin-based therapy in patients with chronic hepatitis C (CHC). We investigated the relationship between IP-10 and treatment response in patients with CHC treated with direct-acting antiviral agents (DAAs) therapy.MethodsWe measured the dynamic changes of IP-10 in samples from 90 patients with CHC. The serum IP-10 levels, intrahepatic expressions of IP-10 mRNA, and protein were determined, respectively. For the in vitro experiments, the expression changes of IP-10 in hepatitis C virus (HCV)-replicating Huh-7 cells with or without non-structural protein 5A (NS5A) inhibitor were analyzed using real-time reverse transcription-polymerase chain reaction and Western blotting.ResultsPatients with chronic hepatitis C had increased baseline IP-10 levels, intrahepatic IP-10 mRNA, and protein expression. After initiating DAAs therapy, serum IP-10 levels decreased gradually in patients who achieved cure, whereas in patients who failed the therapy, IP-10 levels did not change significantly or recovered from the initial decline. Multivariate logistic regression analysis confirmed that baseline IP-10 level ≤ 450 pg/ml and decline >30% at 12 weeks independently predicted the SVR in patients with CHC who received DAAs. In vitro, the expression of IP-10 mRNA and protein in HCV-replicating Huh-7 cells increased significantly. However, such activities were downregulated by NS5A inhibitor, followed by the reduction of HCV RNA levels and a decline in IP-10 levels.ConclusionIP-10 interfered with HCV replication in hepatocytes and the dynamic decline in IP-10 levels during DAA treatment predicted the SVR in patients with CHC.https://www.frontiersin.org/articles/10.3389/fpubh.2022.911551/fullinterferoninterferon-gamma-inducible protein-10direct-acting antiviral agentspegylated interferon alpha/ribavirinhepatitis C virus |
| spellingShingle | Yadong Wang Yangyang Hu Xing Zhang Yue Luo Luyuan Ma Jingjing Lu Qianfei Liang Chengjun Xu Caiyan Zhao Calvin Q. Pan Calvin Q. Pan IP-10 Interferes With the Antiviral Response of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection Frontiers in Public Health interferon interferon-gamma-inducible protein-10 direct-acting antiviral agents pegylated interferon alpha/ribavirin hepatitis C virus |
| title | IP-10 Interferes With the Antiviral Response of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection |
| title_full | IP-10 Interferes With the Antiviral Response of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection |
| title_fullStr | IP-10 Interferes With the Antiviral Response of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection |
| title_full_unstemmed | IP-10 Interferes With the Antiviral Response of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection |
| title_short | IP-10 Interferes With the Antiviral Response of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection |
| title_sort | ip 10 interferes with the antiviral response of direct acting antiviral agents for hepatitis c virus infection |
| topic | interferon interferon-gamma-inducible protein-10 direct-acting antiviral agents pegylated interferon alpha/ribavirin hepatitis C virus |
| url | https://www.frontiersin.org/articles/10.3389/fpubh.2022.911551/full |
| work_keys_str_mv | AT yadongwang ip10interfereswiththeantiviralresponseofdirectactingantiviralagentsforhepatitiscvirusinfection AT yangyanghu ip10interfereswiththeantiviralresponseofdirectactingantiviralagentsforhepatitiscvirusinfection AT xingzhang ip10interfereswiththeantiviralresponseofdirectactingantiviralagentsforhepatitiscvirusinfection AT yueluo ip10interfereswiththeantiviralresponseofdirectactingantiviralagentsforhepatitiscvirusinfection AT luyuanma ip10interfereswiththeantiviralresponseofdirectactingantiviralagentsforhepatitiscvirusinfection AT jingjinglu ip10interfereswiththeantiviralresponseofdirectactingantiviralagentsforhepatitiscvirusinfection AT qianfeiliang ip10interfereswiththeantiviralresponseofdirectactingantiviralagentsforhepatitiscvirusinfection AT chengjunxu ip10interfereswiththeantiviralresponseofdirectactingantiviralagentsforhepatitiscvirusinfection AT caiyanzhao ip10interfereswiththeantiviralresponseofdirectactingantiviralagentsforhepatitiscvirusinfection AT calvinqpan ip10interfereswiththeantiviralresponseofdirectactingantiviralagentsforhepatitiscvirusinfection AT calvinqpan ip10interfereswiththeantiviralresponseofdirectactingantiviralagentsforhepatitiscvirusinfection |