Human MxB Inhibits the Replication of Hepatitis C Virus
| العنوان: | Human MxB Inhibits the Replication of Hepatitis C Virus |
|---|---|
| المؤلفون: | Cheng-Feng Qin, Dongrong Yi, Jing An, Leiliang Zhang, Fengwen Xu, Yongxin Zhang, Jinming Zhou, Zhenlong Liu, Fei Guo, Kavita Raniga, Shan Cen, Xiaoyu Li, Ni An, Chen Liang, Jing Wang, Quanjie Li, Rui Zhou |
| المصدر: | Journal of Virology. 93 |
| بيانات النشر: | American Society for Microbiology, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Myxovirus Resistance Proteins, viruses, Hepatitis C virus, Immunology, Cypa, Hepacivirus, Viral Nonstructural Proteins, Biology, Dengue virus, Endoplasmic Reticulum, Virus Replication, medicine.disease_cause, Microbiology, Virus, Cell Line, 03 medical and health sciences, Flaviviridae, Interferon, Virology, Chlorocebus aethiops, medicine, Animals, Humans, NS5A, Vero Cells, 030304 developmental biology, 0303 health sciences, 030306 microbiology, biology.organism_classification, Virus-Cell Interactions, 3. Good health, HEK293 Cells, Viral replication, Gene Knockdown Techniques, Insect Science, Cyclosporine, Interferons, Cyclophilin A, Protein Binding, medicine.drug |
| الوصف: | Type I interferon (IFN) inhibits viruses by inducing the expression of antiviral proteins. The IFN-induced myxovirus resistance B (MxB) protein has been reported to inhibit a limited number of viruses, including HIV-1 and herpesviruses, but its antiviral coverage remains to be explored further. Here we show that MxB interferes with RNA replication of hepatitis C virus (HCV) and significantly inhibits viral replication in a cyclophilin A (CypA)-dependent manner. Our data further show that MxB interacts with the HCV protein NS5A, thereby impairing NS5A interaction with CypA and NS5A localization to the endoplasmic reticulum, two events essential for HCV RNA replication. Interestingly, we found that MxB significantly inhibits two additional CypA-dependent viruses of the Flaviviridae family, namely, Japanese encephalitis virus and dengue virus, suggesting a potential link between virus dependence on CypA and virus susceptibility to MxB inhibition. Collectively, these data have identified MxB as a key factor behind IFN-mediated suppression of HCV infection, and they suggest that other CypA-dependent viruses may also be subjected to MxB restriction. IMPORTANCE Viruses of the Flaviviridae family cause major illness and death around the world and thus pose a great threat to human health. Here we show that IFN-inducible MxB restricts several members of the Flaviviridae, including HCV, Japanese encephalitis virus, and dengue virus. This finding not only suggests an active role of MxB in combating these major pathogenic human viruses but also significantly expands the antiviral spectrum of MxB. Our study further strengthens the link between virus dependence on CypA and susceptibility to MxB restriction and also suggests that MxB may employ a common mechanism to inhibit different viruses. Elucidating the antiviral functions of MxB advances our understanding of IFN-mediated host antiviral defense and may open new avenues to the development of novel antiviral therapeutics. |
| تدمد: | 1098-5514 0022-538X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::362ce59b0577f5cad140bad88e654ba1Test https://doi.org/10.1128/jvi.01285-18Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....362ce59b0577f5cad140bad88e654ba1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
|---|