Nonstructural NS5A Protein Regulates LIM and SH3 Domain Protein 1 to Promote Hepatitis C Virus Propagation
| العنوان: | Nonstructural NS5A Protein Regulates LIM and SH3 Domain Protein 1 to Promote Hepatitis C Virus Propagation |
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| المؤلفون: | Choi, Jae-Woong, Kim, Jong-Wook, Nguyen, Lap P., Nguyen, Huu C., Park, Eun-Mee, Choi, Dong Hwa, Han, Kang Min, Kang, Sang Min, Tark, Dongseob, Lim, Yun-Sook, Hwang, Soon B. |
| المصدر: | Molecules and Cells |
| بيانات النشر: | Korean Society for Molecular and Cellular Biology, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | hepatitis C virus, Homeodomain Proteins, viruses, Protein Array Analysis, virus diseases, Hepacivirus, LIM Domain Proteins, Viral Nonstructural Proteins, NS5A, Virus Replication, Hepatitis C, digestive system diseases, Cytoskeletal Proteins, HEK293 Cells, Gene Expression Regulation, Protein Domains, protein microarray, Gene Knockdown Techniques, viral replication, Humans, LASP-1, Research Article, Protein Binding |
| الوصف: | Hepatitis C virus (HCV) propagation is highly dependent on cellular proteins. To identify the host factors involved in HCV propagation, we previously performed protein microarray assays and identified the LIM and SH3 domain protein 1 (LASP-1) as an HCV NS5A-interacting partner. LASP-1 plays an important role in the regulation of cell proliferation, migration, and protein-protein interactions. Alteration of LASP-1 expression has been implicated in hepatocellular carcinoma. However, the functional involvement of LASP1 in HCV propagation and HCV-induced pathogenesis has not been elucidated. Here, we first verified the protein interaction of NS5A and LASP-1 by both in vitro pulldown and coimmunoprecipitation assays. We further showed that NS5A and LASP-1 were colocalized in the cytoplasm of HCV infected cells. NS5A interacted with LASP-1 through the proline motif in domain I of NS5A and the tryptophan residue in the SH3 domain of LASP-1. Knockdown of LASP-1 increased HCV replication in both HCV-infected cells and HCV subgenomic replicon cells. LASP-1 negatively regulated viral propagation and thereby overexpression of LASP-1 decreased HCV replication. Moreover, HCV propagation was decreased by wild-type LASP-1 but not by an NS5A binding-defective mutant of LASP-1. We further demonstrated that LASP-1 was involved in the replication stage of the HCV life cycle. Importantly, LASP-1 expression levels were increased in persistently infected cells with HCV. These data suggest that HCV modulates LASP-1 via NS5A in order to regulate virion levels and maintain a persistent infection. |
| اللغة: | English |
| تدمد: | 0219-1032 1016-8478 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid________::a2a96c08711f03085a95672dce98d653Test http://europepmc.org/articles/PMC7264479Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid..........a2a96c08711f03085a95672dce98d653 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 02191032 10168478 |
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