Genetic Adaptation Accompanying the Emergence of Inkoo Virus, the European Orthobunyavirus jamestownense

Inkoo virus (INKV), a member of Orthobunyavirus jamestownense (Jamestown Canyon orthobunyavirus), is widely distributed in northern Europe. Human seroprevalence of INKV is high in endemic areas, and human infection with this agent can cause neurological disease. Here, I deciphered the genetic basis underlying the emergence of the currently circulating INKV in Europe. Phylogenetic analysis showed a clear delineation between the INKV isolates and those of Orthobunyavirus jamestownense from North America and suggested that INKV may be a descendant of an epidemic expansion from America to Europe. Clade model analysis revealed that, compared to the American isolates, INKV has been influenced by different selective pressures, with effects on L protein, surface glycoprotein Gc, and nonstructural protein NSm. Further, contingency analysis showed that, in the emergence of INKV, amino acid changes have accelerated in its L protein and Gc. These changes represent an adaptation likely to local selective pressure. My findings emphasize the significance of endogenous genetic changes in the epidemic dissemination of INKV across geographic space (or the succession of variants) and further highlight the key viral elements and potential mechanisms involved in this process.