Classical swine fever virus non-structural protein 5B hijacks host METTL14-mediated m6A modification to counteract host antiviral immune response.
Classical Swine Fever (CSF), caused by the Classical Swine Fever Virus (CSFV), inflicts significant economic losses on the global pig industry. A key factor in the challenge of eradicating this virus is its ability to evade the host's innate immune response, leading to persistent infections. In...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1012130&type=printable |
| _version_ | 1827262573527957504 |
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| author | Jing Chen Hui-Xin Song Jia-Huan Hu Ji-Shan Bai Xiao-Han Li Rui-Cong Sun Bing-Qian Zhao Mei-Zhen Li Bin Zhou |
| author_facet | Jing Chen Hui-Xin Song Jia-Huan Hu Ji-Shan Bai Xiao-Han Li Rui-Cong Sun Bing-Qian Zhao Mei-Zhen Li Bin Zhou |
| author_sort | Jing Chen |
| collection | DOAJ |
| description | Classical Swine Fever (CSF), caused by the Classical Swine Fever Virus (CSFV), inflicts significant economic losses on the global pig industry. A key factor in the challenge of eradicating this virus is its ability to evade the host's innate immune response, leading to persistent infections. In our study, we elucidate the molecular mechanism through which CSFV exploits m6A modifications to circumvent host immune surveillance, thus facilitating its proliferation. We initially discovered that m6A modifications were elevated both in vivo and in vitro upon CSFV infection, particularly noting an increase in the expression of the methyltransferase METTL14. CSFV non-structural protein 5B was found to hijack HRD1, the E3 ubiquitin ligase for METTL14, preventing METTL14 degradation. MeRIP-seq analysis further revealed that METTL14 specifically targeted and methylated TLRs, notably TLR4. METTL14-mediated regulation of TLR4 degradation, facilitated by YTHDF2, led to the accelerated mRNA decay of TLR4. Consequently, TLR4-mediated NF-κB signaling, a crucial component of the innate immune response, is suppressed by CSFV. Collectively, these data effectively highlight the viral evasion tactics, shedding light on potential antiviral strategies targeting METTL14 to curb CSFV infection. |
| first_indexed | 2024-04-24T09:58:34Z |
| format | Article |
| id | doaj.art-44745840f93c427ea4a62631788d91cd |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2025-03-22T03:16:25Z |
| publishDate | 2024-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-44745840f93c427ea4a62631788d91cd2024-04-30T05:31:29ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-03-01203e101213010.1371/journal.ppat.1012130Classical swine fever virus non-structural protein 5B hijacks host METTL14-mediated m6A modification to counteract host antiviral immune response.Jing ChenHui-Xin SongJia-Huan HuJi-Shan BaiXiao-Han LiRui-Cong SunBing-Qian ZhaoMei-Zhen LiBin ZhouClassical Swine Fever (CSF), caused by the Classical Swine Fever Virus (CSFV), inflicts significant economic losses on the global pig industry. A key factor in the challenge of eradicating this virus is its ability to evade the host's innate immune response, leading to persistent infections. In our study, we elucidate the molecular mechanism through which CSFV exploits m6A modifications to circumvent host immune surveillance, thus facilitating its proliferation. We initially discovered that m6A modifications were elevated both in vivo and in vitro upon CSFV infection, particularly noting an increase in the expression of the methyltransferase METTL14. CSFV non-structural protein 5B was found to hijack HRD1, the E3 ubiquitin ligase for METTL14, preventing METTL14 degradation. MeRIP-seq analysis further revealed that METTL14 specifically targeted and methylated TLRs, notably TLR4. METTL14-mediated regulation of TLR4 degradation, facilitated by YTHDF2, led to the accelerated mRNA decay of TLR4. Consequently, TLR4-mediated NF-κB signaling, a crucial component of the innate immune response, is suppressed by CSFV. Collectively, these data effectively highlight the viral evasion tactics, shedding light on potential antiviral strategies targeting METTL14 to curb CSFV infection.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1012130&type=printable |
| spellingShingle | Jing Chen Hui-Xin Song Jia-Huan Hu Ji-Shan Bai Xiao-Han Li Rui-Cong Sun Bing-Qian Zhao Mei-Zhen Li Bin Zhou Classical swine fever virus non-structural protein 5B hijacks host METTL14-mediated m6A modification to counteract host antiviral immune response. PLoS Pathogens |
| title | Classical swine fever virus non-structural protein 5B hijacks host METTL14-mediated m6A modification to counteract host antiviral immune response. |
| title_full | Classical swine fever virus non-structural protein 5B hijacks host METTL14-mediated m6A modification to counteract host antiviral immune response. |
| title_fullStr | Classical swine fever virus non-structural protein 5B hijacks host METTL14-mediated m6A modification to counteract host antiviral immune response. |
| title_full_unstemmed | Classical swine fever virus non-structural protein 5B hijacks host METTL14-mediated m6A modification to counteract host antiviral immune response. |
| title_short | Classical swine fever virus non-structural protein 5B hijacks host METTL14-mediated m6A modification to counteract host antiviral immune response. |
| title_sort | classical swine fever virus non structural protein 5b hijacks host mettl14 mediated m6a modification to counteract host antiviral immune response |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1012130&type=printable |
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