Moonlighting glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is required for efficient hepatitis C virus and dengue virus infections in human Huh-7.5.1 cells
| العنوان: | Moonlighting glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is required for efficient hepatitis C virus and dengue virus infections in human Huh-7.5.1 cells |
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| المؤلفون: | Meera Raj, François Jean, Mary Langley, Steven J McArthur |
| المصدر: | Journal of General Virology. 98:977-991 |
| بيانات النشر: | Microbiology Society, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, viruses, Hepacivirus, Biology, Dengue virus, Virus Replication, medicine.disease_cause, Cell Line, 03 medical and health sciences, stomatognathic system, Viral envelope, Virology, Gene Knockdown Techniques, medicine, Humans, Glyceraldehyde 3-phosphate dehydrogenase, Host factor, Infectivity, Gene knockdown, Glyceraldehyde-3-Phosphate Dehydrogenases, virus diseases, Dengue Virus, digestive system diseases, 030104 developmental biology, Viral replication, Host-Pathogen Interactions, Hepatocytes, biology.protein |
| الوصف: | Hijacking of cellular biosynthetic pathways by human enveloped viruses is a shared molecular event essential for the viral lifecycle. In this study, the accumulating evidence of the importance of human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the host secretory pathway led us to hypothesize that this moonlighting enzyme could play a key role in the lifecycle steps of two important Flaviviridae members, hepatitis C virus (HCV) and dengue virus (DENV). We used short interfering RNA (siRNA)-mediated knockdown of human GAPDH in Huh-7.5.1 cells- both pre- and post-HCV infection- to demonstrate that GAPDH is a host factor for HCV infection. siRNA-induced GAPDH knockdown performed pre-HCV infection inhibits HCV core production in infected cells and leads to a decrease in infectivity of the HCV-infected cell supernatants. siRNA-induced GAPDH knockdown performed post-HCV infection does not have an effect on HCV core abundance in infected cells, but does lead to a decrease in infectivity of the HCV-infected cell supernatants. Exogenous expression of V5-tagged human GAPDH, pre- and post-infection, increases the infectivity of HCV-infected cell supernatants, suggesting a role for GAPDH during HCV post-replication steps. Interestingly, siRNA-induced GAPDH knockdown in HCV replicon-harbouring cells had no effect on viral RNA replication. Importantly, we confirmed the important role of GAPDH in the HCV lifecycle using Huh-7-derived stable GAPDH-knockdown clones. Finally, siRNA-induced GAPDH knockdown inhibits intracellular DENV-2 E glycoprotein production in infected cells. Collectively, our findings suggest that the moonlighting enzyme, GAPDH, is an important host factor for HCV infection, and they support its potential role in the DENV lifecycle. |
| تدمد: | 1465-2099 0022-1317 |
| DOI: | 10.1099/jgv.0.000754 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b4d67d441e0a723f9afac5b15bf785f https://doi.org/10.1099/jgv.0.000754 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2b4d67d441e0a723f9afac5b15bf785f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14652099 00221317 |
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| DOI: | 10.1099/jgv.0.000754 |