{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:44:34Z","timestamp":1783579474703,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012607","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:00:00Z","timestamp":1727827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["369799452 (TRR237)"],"award-info":[{"award-number":["369799452 (TRR237)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["369799452 (TRR237)"],"award-info":[{"award-number":["369799452 (TRR237)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["390873048 (EXC2151)"],"award-info":[{"award-number":["390873048 (EXC2151)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The RNA genome of orthoflaviviruses encodes a methyltransferase within the non-structural protein NS5, which is involved in 2\u2019-O-methylation of the 5\u2019-terminal nucleotide of the viral genome resulting in a cap1 structure. While a 2\u2019-O-unmethylated cap0 structure is recognized in vertebrates by the RNA sensor RIG-I, the cap1 structure allows orthoflaviviruses to evade the vertebrate innate immune system. Here, we analyzed whether the cap0 structure is also recognized in mosquitoes. Replication analyses of 2\u2019-O-methyltransferase deficient yellow fever virus mutants (YFV NS5-E218A) of the vaccine 17D and the wild-type Asibi strain in mosquito cells revealed a distinct downregulation of the cap0 viruses. Interestingly, the level of inhibition differed for various mosquito cells. The most striking difference was found in <jats:italic>Aedes albopictus<\/jats:italic>-derived C6\/36 cells with YFV-17D cap0 replication being completely blocked. Replication of YFV-Asibi cap0 was also suppressed in mosquito cells but to a lower extent. Analyses using chimeras between YFV-17D and YFV-Asibi suggest that a synergistic effect of several mutations across the viral genome accompanied by a faster initial growth rate of YFV-Asibi cap1 correlates with the lower level of YFV-Asibi cap0 attenuation. Viral growth analyses in Dicer-2 knockout cells demonstrated that Dicer-2 is entirely dispensable for attenuating the YFV cap0 viruses. Translation of a replication-incompetent cap0 reporter YFV-17D genome was reduced in mosquito cells, indicating a cap0 sensing translation regulation mechanism. Further, oral infection of <jats:italic>Aedes aegypti<\/jats:italic> mosquitoes resulted in lower infection rates for YFV-Asibi cap0. The latter is related to lower viral loads found in the midguts, which largely diminished dissemination to secondary tissues. After intrathoracic infection, YFV-Asibi cap0 replicated slower and to decreased amounts in secondary tissues compared to YFV-Asibi cap1. These results suggest the existence of an ubiquitously expressed innate antiviral protein recognizing 5\u2019-terminal RNA cap-modifications in mosquitoes, both in the midgut as well as in secondary tissues.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012607","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T17:33:09Z","timestamp":1727890389000},"page":"e1012607","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["2\u2019-O-methyltransferase-deficient yellow fever virus: Restricted replication in the midgut and secondary tissues of Aedes aegypti mosquitoes severely limits dissemination"],"prefix":"10.1371","volume":"20","author":[{"given":"Anja","family":"vom Hemdt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra L.","family":"Thienel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Ciupka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janett","family":"Wieseler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah M.","family":"Proksch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schlee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9011-2764","authenticated-orcid":true,"given":"Beate M.","family":"K\u00fcmmerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,2]]},"reference":[{"issue":"9","key":"ppat.1012607.ref001","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s00705-023-05835-1","article-title":"Renaming of the genus Flavivirus to Orthoflavivirus and extension of binomial species names within the family Flaviviridae","volume":"168","author":"TS Postler","year":"2023","journal-title":"Arch Virol"},{"issue":"9","key":"ppat.1012607.ref002","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/milmed\/166.suppl_1.55","article-title":"Experimental yellow fever. 1901","volume":"166","author":"W Reed","year":"2001","journal-title":"Mil Med"},{"key":"ppat.1012607.ref003","doi-asserted-by":"crossref","unstructured":"Gershman MD, Staples JE. 64 \u2010 Yellow Fever. 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