A1 Refereed original research article in a scientific journal
Taxonomic expansion and reorganization of Flaviviridae
Authors: Simmonds, Peter; Butković, Anamarija; Grove, Joe; Mayne, Richard; Mifsud, Jonathon C. O.; Beer, Martin; Bukh, Jens; Drexler, J. Felix; Kapoor, Amit; Lohmann, Volker; Smith, Donald B.; Stapleton, Jack T.; Vasilakis, Nikos; Kuhn, Jens H.
Publisher: Springer Nature
Publication year: 2025
Journal: Nature Microbiology
Volume: 10
First page : 3026
Last page: 3037
eISSN: 2058-5276
DOI: https://doi.org/10.1038/s41564-025-02134-0
Publication's open availability at the time of reporting: No Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://doi.org/10.1038/s41564-025-02134-0
Flaviviridae is a family of non-segmented positive-sense RNA viruses that includes major pathogens such as hepatitis C virus, dengue viruses and yellow fever virus. Recent large-scale metagenomic surveys have identified many RNA viruses related to members of this family, such as orthoflaviviruses and pestiviruses. These viruses diverge by having different genome lengths and configurations, and host range. Here we performed an analysis of RNA-directed RNA polymerase (RdRP) hallmark gene sequences of flaviviruses and ‘flavi-like’ viruses. We uncovered four divergent clades and multiple lineages that are congruent with phylogenies of their helicase genes, protein profile hidden Markov model profiles, and evolutionary relationships based on predicted RdRP protein structures. These results support their classification into three families (Flaviviridae, Pestiviridae and Hepaciviridae) and 12 genera in the established order Amarillovirales, with groupings correlating with genome properties and host range. This taxonomy provides a framework for future evolutionary studies on this important viral family.
Funding information in the publication:
N.V. acknowledges partial support from the Centers for Research in Emerging Infectious Diseases (CREID) Coordinating Research on Emerging Arboviral Threats Encompassing the NEOtropics (CREATE-NEO) U01AI151807 grant by the National Institutes of Health (NIH). A.B. was supported by a postdoctoral fellowship from Foundation pour la Recherche Mèdicale (grant number SPF202110014092). J.G. was supported by a Wellcome Trust/Royal Society Sir Henry Dale Fellowship (107653/Z/15/Z) and MRC-University of Glasgow Centre for Virus Research core support from the Medical Research Council (MC_UU_00034/1). J.T.S. was supported by Veterans Administration Merit Review BX000207 and VA SEQCure Network grants.
