Systematic genome analysis enables long-overdue taxonomic reorganization of genus Orthoflavivirus; potential assignment of over 50 new species
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 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 on the basis of 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.
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BibTeX
@misc{simmonds2026systematic,
title = {{Systematic genome analysis enables long-overdue taxonomic reorganization of genus Orthoflavivirus; potential assignment of over 50 new species}},
author = {Peter Simmonds and Martin Beer and Nicolas Bejerman and Jens Bukh and Anamarija Butković and Agathe Colmant and Humberto Debat and J. Felix Drexler and Amit Kapoor and Jens H Kuhn and Volker Lohmann and Donald B Smith and Jack T Stapleton and Nikos Vasilakis},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.21.760428},
url = {https://www.biorxiv.org/content/10.64898/2026.10.21.760428v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Systematic genome analysis enables long-overdue taxonomic reorganization of genus Orthoflavivirus; potential assignment of over 50 new species
AU - Peter Simmonds
AU - Martin Beer
AU - Nicolas Bejerman
AU - Jens Bukh
AU - Anamarija Butković
AU - Agathe Colmant
AU - Humberto Debat
AU - J. Felix Drexler
AU - Amit Kapoor
AU - Jens H Kuhn
AU - Volker Lohmann
AU - Donald B Smith
AU - Jack T Stapleton
AU - Nikos Vasilakis
PY - 2026
DA - 2026/10/21
PB - bioRxiv
DO - 10.64898/2026.10.21.760428
UR - https://www.biorxiv.org/content/10.64898/2026.10.21.760428v1
AB - 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 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 on the basis of 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.
SN - 2692-8205
ER -