Abstract
Crimean-Congo hemorrhagic fever (CCHF) is a zoonosis mainly transmitted by ticks that causes severe hemorrhagic fever and has a mortality rate of 5-60%. The first outbreak of CCHF occurred in the Crimean peninsula in 1944-45 and it has recently emerged in the Balkans and eastern Mediterranean. In order to reconstruct the origin and pathway of the worldwide dispersion of the virus at global and regional (eastern European) level, we investigated the phylogeography of the infection by analysing 121 publicly available CCHFV S gene sequences including two recently characterised Albanian isolates. The spatial and temporal phylogeny was reconstructed using a Bayesian Markov chain Monte Carlo approach, which estimated a mean evolutionary rate of 2.96 x 10-4 (95%HPD=1.6 and 4.7 x 10-4) substitutions/site/year for the analysed fragment. All of the isolates segregated into seven highly significant clades that correspond to the known geographical clades: in particular the two new isolates from northern Albania clustered significantly within the Europe 1 clade. Our phylogeographical reconstruction suggests that the global CCHFV clades originated about one thousand years ago from a common ancestor probably located in Africa. The virus then spread to Asia in the XV century and entered Europe on at least two occasions: the first in the early 1800s, when a still circulating but less or non-pathogenic virus emerged in Greece and Turkey, and the second in the early 1900s, when a pathogenic CCHFV strain began to spread in eastern Europe. The most probable location for the origin of this European clade 1 was Russia, but Turkey played a central role in spreading the virus throughout Europe. Given the close proximity of the infected areas, our data suggest that the movement of wild and domestic ungulates from endemic areas was probably the main cause of the dissemination of the virus in eastern Europe.
Highlights
Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to the family Bunyaviridae, genus Nairovirus
The evaluation of 10,000 randomly chosen quartets showed that only 4.3% fell in the central area of the likelihood map, and 91.8% were at the corners of the triangle, which suggested that the alignment contained sufficient phylogenetic information (Figure S2)
The Europe 1 clade included the majority of the eastern European isolates (Russia, Turkey and a single Greek strain), and contained a monophyletic group consisting of the three sequences from Kosovo and the two new Albanian isolates, whereas the Europe 2 clade isolates encompassed the prototype Greek strain AP92 and five Turkish isolates
Summary
Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to the family Bunyaviridae, genus Nairovirus. It is an enveloped virus with a negative-sense single stranded RNA genome consisting of one small (S), one medium (M) and one large segment (L) that respectively encode the viral nucleocapsid (N), the membrane glycoprotein precursor (GPC), and RNAdependent RNA polymerase (L) proteins [1,2]. The genus Hyalomma, the H. marginatum of Ixodes ticks, is the principal vector of CCHFV, and its geographical distribution correlates with the occurrence of CCHF [4]. In addition to Hyalomma spp., the transmission of CCHFV has been associated with Rhipicephalus (Europe, South Russia), Boophilus (Bulgaria, Russia, Pakistan), Dermacentor (Europe), Ixodes spp. Various wild and domestic mammals act as hosts for feeding ticks that can be infected with the virus; the animal infection is generally asymptomatic
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