Infectious bursal disease virus VP5 triggers host shutoff in a transcription-dependent manner
ABSTRACTViruses have evolved intricate mechanisms to evade host antiviral responses and exploit cellular resources by manipulating the expression profile of host genes. During infection, viruses encode proteins with shutoff activity to globally inhibit host protein synthesis, which is an effective s...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2024-03-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03433-23 |
| _version_ | 1797263289309200384 |
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| author | Xinxin Niu Jinze Han Mengmeng Huang Guodong Wang Yulong Zhang Wenying Zhang Hangbo Yu Mengmeng Xu Kai Li Li Gao Suyan Wang Yuntong Chen Hongyu Cui Yanping Zhang Changjun Liu Xiaomei Wang Yulong Gao Xiaole Qi |
| author_facet | Xinxin Niu Jinze Han Mengmeng Huang Guodong Wang Yulong Zhang Wenying Zhang Hangbo Yu Mengmeng Xu Kai Li Li Gao Suyan Wang Yuntong Chen Hongyu Cui Yanping Zhang Changjun Liu Xiaomei Wang Yulong Gao Xiaole Qi |
| author_sort | Xinxin Niu |
| collection | DOAJ |
| description | ABSTRACTViruses have evolved intricate mechanisms to evade host antiviral responses and exploit cellular resources by manipulating the expression profile of host genes. During infection, viruses encode proteins with shutoff activity to globally inhibit host protein synthesis, which is an effective strategy for immune evasion. In this study, compelling evidence shows that infectious bursal disease virus (IBDV) infection triggers the suppression of host protein synthesis. Furthermore, using both in vitro and in vivo viral infection models, we have identified that IBDV specifically impedes the transcription of host genes via the shutoff activity of viral VP5, simultaneously conferring advantages to IBDV infection in these circumstances. The proposed mechanism suggests that VP5 competitively binds to RanBP1, disrupting the RanGDP/GTP gradient. This disruption interferes with cellular nucleocytoplasmic transport, impairing the nuclear import of proteins bearing nuclear localization signals. The nuclear transport of pivotal transcriptional regulatory factors, such as p65 and IFN regulatory factor 7, is also compromised, leading to the inhibition of pro-inflammatory cytokines and interferon expression. This newly discovered strategy employed by IBDV enables them to manipulate host gene expression, providing novel insights into how viruses evade host immune responses and establish infections.IMPORTANCEViruses manipulate host processes at various levels to regulate or evade both innate and adaptive immune responses, promoting self-survival and efficient transmission. The “host shutoff,” a global suppression of host gene expression mediated by various viruses, is considered a critical mechanism for evading immunity. In this study, we have validated the presence of host shutoff during infectious bursal disease virus (IBDV) infection and additionally uncovered that the viral protein VP5 plays a pivotal role in inhibiting the overall synthesis of host proteins, including cytokines, through a transcription-dependent pathway. VP5 competitively binds with RanBP1, leading to disruption of the Ran protein cycle and consequently interfering with nucleocytoplasmic transport, which ultimately results in the suppression of host gene transcription. These findings unveil a novel strategy employed by IBDV to evade host innate immunity and rapidly establish infection. This study also suggests a novel supplement to understanding the pathway through which viruses inhibit host protein synthesis. |
| first_indexed | 2024-04-25T00:10:38Z |
| format | Article |
| id | doaj.art-d9871c45d9d14cfd9828ea7a9cfc2cda |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-25T00:10:38Z |
| publishDate | 2024-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-d9871c45d9d14cfd9828ea7a9cfc2cda2024-03-13T14:01:05ZengAmerican Society for MicrobiologymBio2150-75112024-03-0115310.1128/mbio.03433-23Infectious bursal disease virus VP5 triggers host shutoff in a transcription-dependent mannerXinxin Niu0Jinze Han1Mengmeng Huang2Guodong Wang3Yulong Zhang4Wenying Zhang5Hangbo Yu6Mengmeng Xu7Kai Li8Li Gao9Suyan Wang10Yuntong Chen11Hongyu Cui12Yanping Zhang13Changjun Liu14Xiaomei Wang15Yulong Gao16Xiaole Qi17Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaAvian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, ChinaABSTRACTViruses have evolved intricate mechanisms to evade host antiviral responses and exploit cellular resources by manipulating the expression profile of host genes. During infection, viruses encode proteins with shutoff activity to globally inhibit host protein synthesis, which is an effective strategy for immune evasion. In this study, compelling evidence shows that infectious bursal disease virus (IBDV) infection triggers the suppression of host protein synthesis. Furthermore, using both in vitro and in vivo viral infection models, we have identified that IBDV specifically impedes the transcription of host genes via the shutoff activity of viral VP5, simultaneously conferring advantages to IBDV infection in these circumstances. The proposed mechanism suggests that VP5 competitively binds to RanBP1, disrupting the RanGDP/GTP gradient. This disruption interferes with cellular nucleocytoplasmic transport, impairing the nuclear import of proteins bearing nuclear localization signals. The nuclear transport of pivotal transcriptional regulatory factors, such as p65 and IFN regulatory factor 7, is also compromised, leading to the inhibition of pro-inflammatory cytokines and interferon expression. This newly discovered strategy employed by IBDV enables them to manipulate host gene expression, providing novel insights into how viruses evade host immune responses and establish infections.IMPORTANCEViruses manipulate host processes at various levels to regulate or evade both innate and adaptive immune responses, promoting self-survival and efficient transmission. The “host shutoff,” a global suppression of host gene expression mediated by various viruses, is considered a critical mechanism for evading immunity. In this study, we have validated the presence of host shutoff during infectious bursal disease virus (IBDV) infection and additionally uncovered that the viral protein VP5 plays a pivotal role in inhibiting the overall synthesis of host proteins, including cytokines, through a transcription-dependent pathway. VP5 competitively binds with RanBP1, leading to disruption of the Ran protein cycle and consequently interfering with nucleocytoplasmic transport, which ultimately results in the suppression of host gene transcription. These findings unveil a novel strategy employed by IBDV to evade host innate immunity and rapidly establish infection. This study also suggests a novel supplement to understanding the pathway through which viruses inhibit host protein synthesis.https://journals.asm.org/doi/10.1128/mbio.03433-23host shutoffnucleocytoplasmic transportRanRanBP1infectious bursal disease virus |
| spellingShingle | Xinxin Niu Jinze Han Mengmeng Huang Guodong Wang Yulong Zhang Wenying Zhang Hangbo Yu Mengmeng Xu Kai Li Li Gao Suyan Wang Yuntong Chen Hongyu Cui Yanping Zhang Changjun Liu Xiaomei Wang Yulong Gao Xiaole Qi Infectious bursal disease virus VP5 triggers host shutoff in a transcription-dependent manner mBio host shutoff nucleocytoplasmic transport Ran RanBP1 infectious bursal disease virus |
| title | Infectious bursal disease virus VP5 triggers host shutoff in a transcription-dependent manner |
| title_full | Infectious bursal disease virus VP5 triggers host shutoff in a transcription-dependent manner |
| title_fullStr | Infectious bursal disease virus VP5 triggers host shutoff in a transcription-dependent manner |
| title_full_unstemmed | Infectious bursal disease virus VP5 triggers host shutoff in a transcription-dependent manner |
| title_short | Infectious bursal disease virus VP5 triggers host shutoff in a transcription-dependent manner |
| title_sort | infectious bursal disease virus vp5 triggers host shutoff in a transcription dependent manner |
| topic | host shutoff nucleocytoplasmic transport Ran RanBP1 infectious bursal disease virus |
| url | https://journals.asm.org/doi/10.1128/mbio.03433-23 |
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