Integrated analysis of protein sequence and structure redefines viral diversity and the taxonomy of the 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:10.1101/2025.01.17.632993

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Integrated analysis of protein sequence and structure redefines viral diversity and the taxonomy of the Flaviviridae

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Integrated analysis of protein sequence and structure redefines viral diversity and the taxonomy of the Flaviviridae

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

bioRxiv

Cold Spring Harbor Laboratory, 1.1

01/18/2025

DOI: 10.1101/2025.01.17.632993

PMCID: PMC11760431

PMID: 39868175

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https://doi.org/10.1101/2025.01.17.632993View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

The Flaviviridae are a family of non-segmented positive-sense enveloped RNA viruses containing significant pathogens including hepatitis C virus and yellow fever virus. Recent large-scale metagenomic surveys have identified many diverse RNA viruses related to classical orthoflaviviruses and pestiviruses but quite different genome lengths and configurations, and with a hugely expanded host range that spans multiple animal phyla, including molluscs, cnidarians and stramenopiles,, and plants. Grouping of RNA-directed RNA polymerase (RdRP) hallmark gene sequences of flavivirus and ‘flavi-like’ viruses into four divergent clades and multiple lineages within them was congruent with helicase gene phylogeny, PPHMM profile comparisons, and comparison of RdRP protein structure predicted by AlphFold2. These results support their classification into the established order, Amarillovirales, in three families (Flaviviridae, Pestiviridae, and Hepaciviridae), and 14 genera. This taxonomic framework informed by RdRP hallmark gene evolutionary relationships provides a stable reference from which major genome re-organisational events can be understood.

Microbiology

Details

Title: Subtitle: Integrated analysis of protein sequence and structure redefines viral diversity and the taxonomy of the 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 - Copenhagen University Hospital
J. Felix Drexler - Humboldt-Universität zu 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: Preprint
Publication Details: bioRxiv
Edition: 1.1
DOI: 10.1101/2025.01.17.632993
PMID: 39868175
PMCID: PMC11760431
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory
Number of pages: 48
Language: English
Date posted: 01/18/2025
Academic Unit: Microbiology and Immunology; Infectious Diseases; Internal Medicine
Record Identifier: 9984781370702771

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