Skip to main content

This is a preprint.

It has not yet been peer reviewed by a journal.

The National Library of Medicine is running a pilot to include preprints that result from research funded by NIH in PMC and PubMed.

bioRxiv logoLink to bioRxiv
[Preprint]. 2026 Oct 25:2026.10.21.760428. [Version 1] doi: 10.64898/2026.10.21.760428

Systematic genome analysis enables long-overdue taxonomic reorganization of genus Orthoflavivirus ; potential assignment of over 50 new species

Peter Simmonds, Martin Beer, Nicolas Bejerman, Jens Bukh, Anamarija Butković, Agathe Colmant, Humberto Debat, J Felix Drexler, Amit Kapoor, Jens H Kuhn, Volker Lohmann, Donald B Smith, Jack T Stapleton, Nikos Vasilakis
PMCID: PMC13738596  PMID: 42996003

Abstract

Members of the Orthoflavivirus genus in the family Flaviviridae are primarily vector-transmitted RNA viruses infecting humans, other mammals and birds, including major pathogens such as tick borne encephalitis, West Nile, Zika, yellow fever and dengue viruses. Vector-borne flaviviruses are assigned to the Euflavivirus subgenus of orthoflaviviruses, with more divergent largely unclassified insect-specific flaviviruses, including cell fusing agent virus assigned to the second subgenus, Fusivirus . The currently classified 57 orthoflavivirus species have traditionally been assigned descriptively based on their genome and antigenic relatedness, ecology and host and vector tropisms, although many more orthoflavi-like viruses remain unassigned. To investigate whether species might be demarcated using a fixed genetic divergence threshold, we examined distributions of pairwise distances in NS5 and E genes (which encode the RNA-dependent RNA polymerase and envelope protein, respectively) of classified orthoflaviviruses. Demarcation thresholds of 0.1 in the two regions would be most parsimonious with current euflavivirus classification. Exceptions include species in the tick-borne encephalitis virus complex with divergences below the threshold, and dengue virus types currently assigned to a single species that are substantially above. Application of the proposed thresholds would provide the means to establish 25 new euflavivirus and 33 new fusivirus species and reconcile several anomalies and inconsistencies in the current species taxonomy. The use of a species demarcation threshold brings consistency with the classification of viruses in other families. A robust and evolutionarily consistent framework furthermore enables taxonomic assignments of the numerous currently unassigned orthoflaviviruses that lack the phenotypic descriptions required for the current species definition.

Full Text

The Full Text of this preprint is available as a PDF (1.6 MB). The Web version will be available soon.


Articles from bioRxiv are provided here courtesy of Cold Spring Harbor Laboratory Preprints

RESOURCES