N6-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses
ABSTRACTN6-methyladenosine (m6A) is one of the most abundant modifications of cellular RNA, where it serves various functions. m6A methylation of many viral RNA species has also been described; however, little is known about the m6A epitranscriptome of haemorrhagic fever-causing viruses like Ebola v...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2223732 |
| _version_ | 1797257053704552448 |
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| author | Lisa Wendt Matthew J. Pickin Bianca S. Bodmer Sven Reiche Lucie Fénéant Julia E. Hölper Walter Fuchs Allison Groseth Thomas Hoenen |
| author_facet | Lisa Wendt Matthew J. Pickin Bianca S. Bodmer Sven Reiche Lucie Fénéant Julia E. Hölper Walter Fuchs Allison Groseth Thomas Hoenen |
| author_sort | Lisa Wendt |
| collection | DOAJ |
| description | ABSTRACTN6-methyladenosine (m6A) is one of the most abundant modifications of cellular RNA, where it serves various functions. m6A methylation of many viral RNA species has also been described; however, little is known about the m6A epitranscriptome of haemorrhagic fever-causing viruses like Ebola virus (EBOV). Here, we analysed the importance of the methyltransferase METTL3 for the life cycle of this virus. We found that METTL3 interacts with the EBOV nucleoprotein and the transcriptional activator VP30 to support viral RNA synthesis, and that METTL3 is recruited into EBOV inclusions bodies, where viral RNA synthesis occurs. Analysis of the m6A methylation pattern of EBOV mRNAs showed that they are methylated by METTL3. Further studies revealed that METTL3 interaction with the viral nucleoprotein, as well as its importance for RNA synthesis and protein expression, is also observed for other haemorrhagic fever viruses such as Junín virus (JUNV) and Crimean-Congo haemorrhagic fever virus (CCHFV). The negative effects on viral RNA synthesis due to loss of m6A methylation are independent of innate immune sensing, as METTL3 knockout did not affect type I interferon induction in response to viral RNA synthesis or infection. Our results suggest a novel function for m6A that is conserved among diverse haemorrhagic fever-causing viruses (i.e. EBOV, JUNV and CCHFV), making METTL3 a promising target for broadly-acting antivirals. |
| first_indexed | 2024-03-08T11:51:23Z |
| format | Article |
| id | doaj.art-62c5266ddb584950a551e67cafce10d7 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-04-24T22:31:32Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-62c5266ddb584950a551e67cafce10d72024-03-19T19:34:17ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2223732N6-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever virusesLisa Wendt0Matthew J. Pickin1Bianca S. Bodmer2Sven Reiche3Lucie Fénéant4Julia E. Hölper5Walter Fuchs6Allison Groseth7Thomas Hoenen8Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, GermanyInstitute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, GermanyInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, GermanyDepartment of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, GermanyInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, GermanyInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, GermanyInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, GermanyInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, GermanyInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, GermanyABSTRACTN6-methyladenosine (m6A) is one of the most abundant modifications of cellular RNA, where it serves various functions. m6A methylation of many viral RNA species has also been described; however, little is known about the m6A epitranscriptome of haemorrhagic fever-causing viruses like Ebola virus (EBOV). Here, we analysed the importance of the methyltransferase METTL3 for the life cycle of this virus. We found that METTL3 interacts with the EBOV nucleoprotein and the transcriptional activator VP30 to support viral RNA synthesis, and that METTL3 is recruited into EBOV inclusions bodies, where viral RNA synthesis occurs. Analysis of the m6A methylation pattern of EBOV mRNAs showed that they are methylated by METTL3. Further studies revealed that METTL3 interaction with the viral nucleoprotein, as well as its importance for RNA synthesis and protein expression, is also observed for other haemorrhagic fever viruses such as Junín virus (JUNV) and Crimean-Congo haemorrhagic fever virus (CCHFV). The negative effects on viral RNA synthesis due to loss of m6A methylation are independent of innate immune sensing, as METTL3 knockout did not affect type I interferon induction in response to viral RNA synthesis or infection. Our results suggest a novel function for m6A that is conserved among diverse haemorrhagic fever-causing viruses (i.e. EBOV, JUNV and CCHFV), making METTL3 a promising target for broadly-acting antivirals.https://www.tandfonline.com/doi/10.1080/22221751.2023.2223732Ebola virusJunín virusCrimean-Congo haemorrhagic fever virusfilovirusarenavirusorthonairovirus |
| spellingShingle | Lisa Wendt Matthew J. Pickin Bianca S. Bodmer Sven Reiche Lucie Fénéant Julia E. Hölper Walter Fuchs Allison Groseth Thomas Hoenen N6-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses Emerging Microbes and Infections Ebola virus Junín virus Crimean-Congo haemorrhagic fever virus filovirus arenavirus orthonairovirus |
| title | N6-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses |
| title_full | N6-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses |
| title_fullStr | N6-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses |
| title_full_unstemmed | N6-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses |
| title_short | N6-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses |
| title_sort | n6 methyladenosine is required for efficient rna synthesis of ebola virus and other haemorrhagic fever viruses |
| topic | Ebola virus Junín virus Crimean-Congo haemorrhagic fever virus filovirus arenavirus orthonairovirus |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2223732 |
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