Taxonomic expansion and reorganization of Flaviviridae

Peter Simmonds; Anamarija Butković; Joe Grove; Richard Mayne; Jonathon C O Mifsud; Martin Beer; Jens Bukh; J Felix Drexler; Amit Kapoor; Volker Lohmann; Donald B Smith; Jack T Stapleton; Nikos Vasilakis; Jens H Kuhn

doi:10.1038/s41564-025-02134-0

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Taxonomic expansion and reorganization of Flaviviridae

Journal article

Peer reviewed

Taxonomic expansion and reorganization of Flaviviridae

Peter Simmonds, Anamarija Butković, Joe Grove, Richard Mayne, Jonathon C O Mifsud, Martin Beer, Jens Bukh, J Felix Drexler, Amit Kapoor, Volker Lohmann, …

Nature microbiology, Vol.10(11), pp.3026-3037

11/2025

DOI: 10.1038/s41564-025-02134-0

PMID: 41174177

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Abstract

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.

Evolution, Molecular

Flaviviridae - classification

Flaviviridae - enzymology

Flaviviridae - genetics

Genome, Viral

Host Specificity

Phylogeny

RNA Helicases - genetics

RNA-Dependent RNA Polymerase - genetics

Viral Proteins - genetics

Details

Title: Subtitle: Taxonomic expansion and reorganization of Flaviviridae
Creators: Peter Simmonds - University of Oxford
Anamarija Butković - Université Paris Cité
Joe Grove - MRC University of Glasgow Centre for Virus Research
Richard Mayne - University of Oxford
Jonathon C O Mifsud - Taronga Conservation Society Australia
Martin Beer - Friedrich-Loeffler-Institut
Jens Bukh - University of Copenhagen
J Felix Drexler - Charité - Universitätsmedizin Berlin
Amit Kapoor - Nationwide Children's Hospital
Volker Lohmann - Heidelberg University
Donald B Smith - University of Oxford
Jack T Stapleton - Iowa City VA Health Care System
Nikos Vasilakis - The University of Texas Medical Branch at Galveston
Jens H Kuhn - National Institute of Allergy and Infectious Diseases
Resource Type: Journal article
Publication Details: Nature microbiology, Vol.10(11), pp.3026-3037
DOI: 10.1038/s41564-025-02134-0
PMID: 41174177
NLM abbreviation: Nat Microbiol
ISSN: 2058-5276
eISSN: 2058-5276
Publisher: NATURE PORTFOLIO
Grant note: 107653/Z/15/Z / Wellcome Trust (Wellcome) MC_UU_00034/1 / Department of Health | National Health and Medical Research Council (NHMRC) NIHR203338) / DH | National Institute for Health Research (NIHR)
Language: English
Date published: 11/2025
Academic Unit: Microbiology and Immunology; Infectious Diseases; Internal Medicine
Record Identifier: 9985024165702771

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