Discovery of influenza-like virus clades in invertebrates and the evolutionary history and host-shifting events of Orthomyxoviridae in metazoans.

Epidemics are often initiated by emerging and re-emerging infectious diseases caused by viruses of animal origin. It is thus important to identify the reservoirs of potentially zoonotic viruses and understand the dynamics of their host shifts. The flu viruses belong to the virus family Orthomyxoviridae, which also contains Isavirus, Quaranjavirus, and Thogotovirus. Many members of this virus family are known to be pathogenic to humans. For initial surveillance of animal-originated or zoonotic Orthomyxoviridae, unclassified viruses were screened by the use of high-throughput transcriptomes as a data source because of their wide species and lineage coverage. We identified 96 novel or unclassified Orthomyxoviridae members with the discovery of three new lineages of the virus, possibly new genera, one sister to Influenza + Thogotovirus, one to Influenza + Thogotovirus + Quaranjavirus, and another one to all orthomyxoviruses except Isavirus. Throughout the evolution of Orthomyxoviridae, there might be multiple host-shifting incidences, shifting between six different animal host phyla. The most common host shifts seemed to be between Arthropoda and Chordata; however, further evidence would be needed to fully support this statement. Nonetheless, Orthomyxoviridae viruses can infect a wide range of animal phyla, while some members hold a higher risk of shifting back to Chordates and humans that warrants surveillance.