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

Abstract

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.