Endoplasmic Reticulum-Associated Degradation Controls Virus Protein Homeostasis, Which Is Required for Flavivirus Propagation
| العنوان: | Endoplasmic Reticulum-Associated Degradation Controls Virus Protein Homeostasis, Which Is Required for Flavivirus Propagation |
|---|---|
| المؤلفون: | Atsuki Nara, Takehiro Sugimoto, Makiko Kobayashi, Keisuke Tabata, Kotaro Ishida, Masashi Arakawa, Eiji Morita, Tetsuya Okada, Kazutoshi Mori |
| المصدر: | J Virol |
| بيانات النشر: | American Society for Microbiology, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Viral protein, Ubiquitin-Protein Ligases, viruses, Immunology, Genome, Viral, Viral Nonstructural Proteins, Endoplasmic-reticulum-associated protein degradation, Biology, Dengue virus, Endoplasmic Reticulum, Virus Replication, medicine.disease_cause, Microbiology, Virus, 03 medical and health sciences, Valosin Containing Protein, Cell Line, Tumor, Virology, Chlorocebus aethiops, medicine, Animals, Humans, RNA, Small Interfering, Vero Cells, 030304 developmental biology, Encephalitis Virus, Japanese, 0303 health sciences, Endoplasmic reticulum, 030302 biochemistry & molecular biology, Membrane Proteins, Proteins, Endoplasmic Reticulum-Associated Degradation, Dengue Virus, HCT116 Cells, biology.organism_classification, Virus-Cell Interactions, Cell biology, Flavivirus, HEK293 Cells, Viral replication, Insect Science, RNA Interference, Viral genome replication, HeLa Cells |
| الوصف: | Many positive-stranded RNA viruses encode polyproteins from which viral proteins are generated by processing the polyproteins. This system produces an equal amount of each viral protein, though the required amounts for each protein are not the same. In this study, we found the extra membrane-anchored nonstructural (NS) proteins of Japanese encephalitis virus and dengue virus are rapidly and selectively degraded by the endoplasmic reticulum-associated degradation (ERAD) pathway. Our gene targeting study revealed that ERAD involving Derlin2 and SEL1L, but not Derlin1, is required for the viral genome replication. Derlin2 is predominantly localized in the convoluted membrane (CM) of the viral replication organelle, and viral NS proteins are degraded in the CM. Hence, these results suggest that viral protein homeostasis is regulated by Derlin2-mediated ERAD in the CM, and this process is critical for the propagation of these viruses. IMPORTANCE The results of this study reveal the cellular ERAD system controls the amount of each viral protein in virus-infected cells and that this “viral protein homeostasis” is critical for viral propagation. Furthermore, we clarified that the “convoluted membrane (CM),” which was previously considered a structure with unknown function, serves as a kind of waste dump where viral protein degradation occurs. We also found that the Derlin2/SEL1L/HRD1-specific pathway is involved in this process, whereas the Derlin1-mediated pathway is not. This novel ERAD-mediated fine-tuning system for the stoichiometries of polyprotein-derived viral proteins may represent a common feature among polyprotein-encoding viruses. |
| تدمد: | 1098-5514 0022-538X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::921bc0bfaaa65bd5f2d73863c6df1b73Test https://doi.org/10.1128/jvi.02234-20Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....921bc0bfaaa65bd5f2d73863c6df1b73 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
|---|