Abl Tyrosine Kinase Regulates Hepatitis C Virus Entry
Abl is a central regulator of multiple cellular processes controlling actin dynamics, proliferation, and differentiation. Here, we showed that knockdown of Abl impaired hepatitis C virus (HCV) propagation. Treatment of Abl tyrosine kinase-specific inhibitor, imatinib and dasatinib, also significantl...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2017-06-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2017.01129/full |
| _version_ | 1811317095586070528 |
|---|---|
| author | Saehong Min Saehong Min Yun-Sook Lim Dongjo Shin Dongjo Shin Chorong Park Chorong Park Jae-Bong Park Seungtaek Kim Marc P. Windisch Soon B. Hwang Soon B. Hwang |
| author_facet | Saehong Min Saehong Min Yun-Sook Lim Dongjo Shin Dongjo Shin Chorong Park Chorong Park Jae-Bong Park Seungtaek Kim Marc P. Windisch Soon B. Hwang Soon B. Hwang |
| author_sort | Saehong Min |
| collection | DOAJ |
| description | Abl is a central regulator of multiple cellular processes controlling actin dynamics, proliferation, and differentiation. Here, we showed that knockdown of Abl impaired hepatitis C virus (HCV) propagation. Treatment of Abl tyrosine kinase-specific inhibitor, imatinib and dasatinib, also significantly decreased HCV RNA and protein levels in HCV-infected cells. We showed that both imatinib and dasatinib selectively inhibited HCV infection at the entry step of HCV life cycle, suggesting that Abl kinase activity may be necessary for HCV entry. Using HCV pseudoparticle infection assays, we verified that Abl is required for viral entry. By employing transferrin uptake and immunofluorescence assays, we further demonstrated that Abl was involved in HCV entry at a clathrin-mediated endocytosis step. These data suggest that Abl may represent a novel host factor for HCV entry. |
| first_indexed | 2024-04-13T12:00:32Z |
| format | Article |
| id | doaj.art-7d55f83173bb49e5aaa9993b879c9ecb |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T12:00:32Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-7d55f83173bb49e5aaa9993b879c9ecb2022-12-22T02:47:47ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2017-06-01810.3389/fmicb.2017.01129266003Abl Tyrosine Kinase Regulates Hepatitis C Virus EntrySaehong Min0Saehong Min1Yun-Sook Lim2Dongjo Shin3Dongjo Shin4Chorong Park5Chorong Park6Jae-Bong Park7Seungtaek Kim8Marc P. Windisch9Soon B. Hwang10Soon B. Hwang11Department of Biomedical Gerontology, Graduate School of Hallym UniversityChuncheon, South KoreaNational Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym UniversityAnyang, South KoreaNational Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym UniversityAnyang, South KoreaDepartment of Biomedical Gerontology, Graduate School of Hallym UniversityChuncheon, South KoreaHepatitis Research Laboratory, Institut Pasteur KoreaSeongnam, South KoreaDepartment of Biomedical Gerontology, Graduate School of Hallym UniversityChuncheon, South KoreaNational Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym UniversityAnyang, South KoreaDepartment of Biochemistry, College of Medicine, Hallym UniversityChuncheon, South KoreaInstitute of Gastroenterology, Yonsei University College of MedicineSeoul, South KoreaHepatitis Research Laboratory, Institut Pasteur KoreaSeongnam, South KoreaDepartment of Biomedical Gerontology, Graduate School of Hallym UniversityChuncheon, South KoreaNational Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym UniversityAnyang, South KoreaAbl is a central regulator of multiple cellular processes controlling actin dynamics, proliferation, and differentiation. Here, we showed that knockdown of Abl impaired hepatitis C virus (HCV) propagation. Treatment of Abl tyrosine kinase-specific inhibitor, imatinib and dasatinib, also significantly decreased HCV RNA and protein levels in HCV-infected cells. We showed that both imatinib and dasatinib selectively inhibited HCV infection at the entry step of HCV life cycle, suggesting that Abl kinase activity may be necessary for HCV entry. Using HCV pseudoparticle infection assays, we verified that Abl is required for viral entry. By employing transferrin uptake and immunofluorescence assays, we further demonstrated that Abl was involved in HCV entry at a clathrin-mediated endocytosis step. These data suggest that Abl may represent a novel host factor for HCV entry.http://journal.frontiersin.org/article/10.3389/fmicb.2017.01129/fullhepatitis C virusAbl tyrosine kinasehost factorHCV entrytyrosine kinase- inhibitorviral propagation |
| spellingShingle | Saehong Min Saehong Min Yun-Sook Lim Dongjo Shin Dongjo Shin Chorong Park Chorong Park Jae-Bong Park Seungtaek Kim Marc P. Windisch Soon B. Hwang Soon B. Hwang Abl Tyrosine Kinase Regulates Hepatitis C Virus Entry Frontiers in Microbiology hepatitis C virus Abl tyrosine kinase host factor HCV entry tyrosine kinase- inhibitor viral propagation |
| title | Abl Tyrosine Kinase Regulates Hepatitis C Virus Entry |
| title_full | Abl Tyrosine Kinase Regulates Hepatitis C Virus Entry |
| title_fullStr | Abl Tyrosine Kinase Regulates Hepatitis C Virus Entry |
| title_full_unstemmed | Abl Tyrosine Kinase Regulates Hepatitis C Virus Entry |
| title_short | Abl Tyrosine Kinase Regulates Hepatitis C Virus Entry |
| title_sort | abl tyrosine kinase regulates hepatitis c virus entry |
| topic | hepatitis C virus Abl tyrosine kinase host factor HCV entry tyrosine kinase- inhibitor viral propagation |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2017.01129/full |
| work_keys_str_mv | AT saehongmin abltyrosinekinaseregulateshepatitiscvirusentry AT saehongmin abltyrosinekinaseregulateshepatitiscvirusentry AT yunsooklim abltyrosinekinaseregulateshepatitiscvirusentry AT dongjoshin abltyrosinekinaseregulateshepatitiscvirusentry AT dongjoshin abltyrosinekinaseregulateshepatitiscvirusentry AT chorongpark abltyrosinekinaseregulateshepatitiscvirusentry AT chorongpark abltyrosinekinaseregulateshepatitiscvirusentry AT jaebongpark abltyrosinekinaseregulateshepatitiscvirusentry AT seungtaekkim abltyrosinekinaseregulateshepatitiscvirusentry AT marcpwindisch abltyrosinekinaseregulateshepatitiscvirusentry AT soonbhwang abltyrosinekinaseregulateshepatitiscvirusentry AT soonbhwang abltyrosinekinaseregulateshepatitiscvirusentry |