Molecular Epidemiology of Crimean-Congo Hemorrhagic Fever Virus in Kosovo

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a zoonotic agent that causes severe, life-threatening disease, with a case fatality rate of 10–50%. It is the most widespread tick-borne virus in the world, with cases reported in Africa, Asia and Eastern Europe. CCHFV is a genetically diverse virus. Its genetic diversity is often correlated to its geographical origin. Genetic variability of CCHFV was determined within few endemic areas, however limited data is available for Kosovo. Furthermore, there is little information about the spatiotemporal genetic changes of CCHFV in endemic areas. Kosovo is an important endemic area for CCHFV. Cases were reported each year and the case-fatality rate is significantly higher compared to nearby regions. In this study, we wanted to examine the genetic variability of CCHFV obtained directly from CCHF-confirmed patients, hospitalized in Kosovo from 1991 to 2013. We sequenced partial S segment CCHFV nucleotide sequences from 89 patients. Our results show that several viral variants are present in Kosovo and that the genetic diversity is high in relation to the studied area. We also show that variants are mostly uniformly distributed throughout Kosovo and that limited evolutionary changes have occurred in 22 years. Our results also suggest the presence of a new distinct lineage within the European CCHF phylogenetic clade. Our study provide the largest number of CCHFV nucleotide sequences from patients in 22 year span in one endemic area.

Serological and Virological Evidence of Crimean-Congo Haemorrhagic Fever Virus Circulation in the Human Population of Borno State, Northeastern Nigeria

“…It is interesting that despite being isolated 50 years ago from a tick, there is remarkable similarity in these Nigerian viruses. Analogous observations have been made in the past [41,42], illustrating that CCHFV can be genetically very stable over long periods of time, while on other occasions there is vast genetic variation between strains, even between those sequenced from similar locations [43]. Such observations may point to the broader ecological conditions which support the virus-host environment; highly changeable ecologies resulting in more opportunities for CCHF viruses to exploit new sequence space, whereas stable ecological conditions would restrict diversity.…”

Crimean-Congo Hemorrhagic Fever Virus Clades V and VI (Europe 1 and 2) in Ticks in Kosovo, 2012

“…This narrows down estimates from previous results, which calculated the existence of a common ancestor between 700 and 1000 years [7], [39]. The differences may be due to the large number of strains (n = 270) used in our study, resulting in a more robust time-resolved phylogenetic estimation.…”

Dual RNA-Seq characterization of host and pathogen gene expression in liver cells infected with Crimean-Congo Hemorrhagic Fever Virus

“…A limitation of our study is the use of the prototypical IbAr 10200 strain, which has undergone significant passaging and lab adaptation and is likely more attenuated than currently circulating strains [9,52]. Although use of this strain permits comparison to other laboratory findings (due to it's widespread use in Western labs), further studies to compare transcriptomic profiles from CCHFV strains associated with low mortality, such as AP92, to more virulent isolates, performed in both cell lines and primary cell cultures are needed to provide additional insight into viral pathogenesis [53][54][55].…”