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A well-known challenge in the development of a live attenuated RSV vaccine is that interferon (IFN)-mediated antiviral responses are strongly suppressed by RSV nonstructural proteins which, in turn, dampens the subsequent adaptive immune responses. Here, we discovered a novel strategy to enhance innate and adaptive immunity to RSV infection. Specifically, we found that recombinant RSVs deficient in viral RNA <jats:italic>N<\/jats:italic><jats:sup>6<\/jats:sup>-methyladenosine (m<jats:sup>6<\/jats:sup>A) and RSV grown in m<jats:sup>6<\/jats:sup>A methyltransferase (METTL3)-knockdown cells induce higher expression of RIG-I, bind more efficiently to RIG-I, and enhance RIG-I ubiquitination and IRF3 phosphorylation compared to wild-type virion RNA, leading to enhanced type I IFN production. Importantly, these m<jats:sup>6<\/jats:sup>A-deficient RSV mutants also induce a stronger IFN response in vivo, are significantly attenuated, induce higher neutralizing antibody and T cell immune responses in mice and provide complete protection against RSV challenge in cotton rats. Collectively, our results demonstrate that inhibition of RSV RNA m<jats:sup>6<\/jats:sup>A methylation enhances innate immune responses which in turn promote adaptive immunity.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010142","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T18:59:49Z","timestamp":1640026789000},"page":"e1010142","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":44,"title":["Viral RNA N6-methyladenosine modification modulates both innate and adaptive immune responses of human respiratory syncytial virus"],"prefix":"10.1371","volume":"17","author":[{"given":"Miaoge","family":"Xue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexiu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth 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Domachowske","year":"1999","journal-title":"Clin Microbiol Rev"},{"issue":"39","key":"ppat.1010142.ref058","doi-asserted-by":"crossref","first-page":"14999","DOI":"10.1073\/pnas.0802555105","article-title":"Respiratory syncytial virus impairs T cell activation by preventing synapse assembly with dendritic cells","volume":"105","author":"PA Gonzalez","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"ppat.1010142.ref059","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41579-020-0382-3","article-title":"Epigenetic and epitranscriptomic regulation of viral replication","volume":"18","author":"K Tsai","year":"2020","journal-title":"Nat Rev Microbiol"},{"issue":"3","key":"ppat.1010142.ref060","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.chom.2017.08.004","article-title":"Epitranscriptomic Enhancement of Influenza A Virus Gene Expression and Replication.","volume":"22","author":"DG Courtney","year":"2017","journal-title":"Cell 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Connors","year":"1994","journal-title":"Journal of Virology"},{"issue":"1","key":"ppat.1010142.ref070","first-page":"31","article-title":"Characterization of Cotton Rat (Sigmodon hispidus) Eosinophils, Including Their Response to Respiratory Syncytial Virus Infection.","volume":"68","author":"MG Green","year":"2018","journal-title":"Comparative Med."},{"issue":"2","key":"ppat.1010142.ref071","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/s41590-018-0275-z","article-title":"m(6)A modification controls the innate immune response to infection by targeting type I interferons.","volume":"20","author":"R Winkler","year":"2019","journal-title":"Nat Immunol"},{"issue":"23\u201324","key":"ppat.1010142.ref072","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1101\/gad.319475.118","article-title":"RNA m(6) A modification enzymes shape innate responses to DNA by regulating interferon beta.","volume":"32","author":"RM Rubio","year":"2018","journal-title":"Genes Dev"},{"issue":"6","key":"ppat.1010142.ref073","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.immuni.2020.05.003","article-title":"A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development","volume":"52","author":"Y Gao","year":"2020","journal-title":"Immunity"},{"issue":"9","key":"ppat.1010142.ref074","article-title":"Nonsegmented Negative-Sense RNA Viruses Utilize N (6)-Methyladenosine (m(6)A) as a Common Strategy To Evade Host Innate Immunity.","volume":"95","author":"M Lu","year":"2021","journal-title":"J Virol"},{"issue":"6","key":"ppat.1010142.ref075","doi-asserted-by":"crossref","first-page":"109091","DOI":"10.1016\/j.celrep.2021.109091","article-title":"METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection.","volume":"35","author":"N Li","year":"2021","journal-title":"Cell Rep."},{"issue":"22","key":"ppat.1010142.ref076","doi-asserted-by":"crossref","first-page":"10508","DOI":"10.1128\/JVI.74.22.10508-10513.2000","article-title":"Glycosaminoglycan sulfation requirements for respiratory syncytial virus infection","volume":"74","author":"LK Hallak","year":"2000","journal-title":"J Virol"},{"issue":"15","key":"ppat.1010142.ref077","doi-asserted-by":"crossref","first-page":"6825","DOI":"10.1128\/JVI.75.15.6825-6834.2001","article-title":"Functional analysis of recombinant respiratory syncytial virus deletion mutants lacking the small hydrophobic and\/or attachment glycoprotein gene","volume":"75","author":"S Techaarpornkul","year":"2001","journal-title":"J Virol"},{"issue":"25","key":"ppat.1010142.ref078","doi-asserted-by":"crossref","first-page":"11563","DOI":"10.1073\/pnas.92.25.11563","article-title":"Production of infectious human respiratory syncytial virus from cloned cDNA confirms an essential role for the transcription elongation factor from the 5\u2019 proximal open reading frame of the M2 mRNA in gene expression and provides a capability for vaccine development","volume":"92","author":"PL Collins","year":"1995","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"ppat.1010142.ref079","article-title":"Nonsegmented Negative-Sense RNA Viruses Utilize N-6-Methyladenosine (m(6)A) as a Common Strategy To Evade Host Innate Immunity.","volume":"95","author":"MJ Lu","year":"2021","journal-title":"J Virol"},{"issue":"24","key":"ppat.1010142.ref080","article-title":"Stable Attenuation of Human Respiratory Syncytial Virus for Live Vaccines by Deletion and Insertion of Amino Acids in the Hinge Region between the mRNA Capping and Methyltransferase Domains of the Large Polymerase Protein","volume":"94","author":"MG Xue","year":"2020","journal-title":"J Virol"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010142","type":"new_version","label":"New 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