Genetic Diversification of Crimean-Congo Hemorrhagic Fever Virus Lineage Europe 1

Crimean-Congo hemorrhagic fever (CCHF) is prevalent in Africa, Asia, and Europe and poses a serious and long-standing public health burden. Europe, especially Russia, Turkey, and the Balkan region, has been a hotspot for the disease, with the most confirmed reports. Crimean-Congo hemorrhagic fever virus (CCHFV), the etiological agent of the disease, shows general delineation of phylogeography among the CCHF-epidemic areas. The isolates of lineage Europe 1 represent the majority of the agent in Europe and primarily circulate in the Russia-Turkey-Balkan region. To decipher the molecular basis of the CCHF epidemicity in Europe, I analyzed the genetic diversification of lineage Europe 1 isolates. Contingency analysis with the reconstructed ancestral sequences of the large (L) and medium (M) segments showed that, in the early epidemic of the lineage, rapid diversification occurred in the nonstructural M protein of the M segment. The McDonald-Kreitman test, together with contingency analysis, showed that nucleoprotein of the small (S) segment achieved an acceleration of amino acid substitutions in this process. These findings offer a molecular perspective on CCHFV epidemicity, at least in Europe, and highlight the key viral factors that could have contributed to the emergence of lineage Europe 1.