Virology The<unk>  orthonairovirus (CCHFV) is a member of the genus Orthonairovirus, family Nairoviridae of RNA viruses. The virions are 80–120 nanometers (nm) in diameter and are pleomorphic. There are no host ribosomes within the virion. Each virion contains three distinct RNA sequences, which together make up the viral genome. The envelope is single layered and is formed from a lipid bilayer 5 nm thick. It has no external protrusions. The envelope proteins form small projections ~5–10 nm long. The nucleocapsids are filamentous and circular with a length of 200–3000 nm. Viral entry is thought to be clathrin-mediated with the cell surface protein nucleolin playing a role. Molecular biology The genome is circular, negative sense RNA in three parts<unk>  Small (S), Medium (M) and Large (L). The L segment is 11–14.4 kilobases in length while the M and S segments are 4.4–6.3 and 1.7–2.1 kilobases long respectively. The L segment encodes the RNA polymerase, the M segment encodes the envelope glycoproteins (Gc and Gn), and the S segment encodes the nucleocapsid protein. The mutation rates for the three parts of the genome were estimated to be: 1.09, 1.52 and 0.58 substitutions/site/year for the S, M, and L segments respectively. Population genetics CCHFV is the most genetically diverse of the arboviruses: Its nucleotide sequences frequently differ between different strains, ranging from a 20% variability for the viral S segment to 31% for the M segment. Viruses with diverse sequences can be found within the same geographic area; closely related viruses have been isolated from widely separated regions, suggesting that viral dispersion has occurred possibly by ticks carried on migratory birds or through international livestock trade. Reassortment among genome segments during coinfection of ticks or vertebrates seems likely to have played a role in generating diversity in this virus. Based on the sequence data, seven genotypes of CCHFV have been recognised: Africa 1 (Senegal), Africa 2 (Democratic Republic of the<unk>  and South Africa), Africa 3 (southern and western Africa), Europe 1 (Albania, Bulgaria, Kosovo, Russia and Turkey), Europe 2 (Greece), Asia 1 (the Middle East, Iran and Pakistan) and Asia 2 (China, Kazakhstan, Tajikistan and Uzbekistan). Transmission Hyalomma tick Ticks are both "environmental reservoir" and vector for the virus, carrying it from wild animals to domestic animals and humans. Tick species identified as infected with the virus include Argas reflexus, Hyalomma anatolicum, Hyalomma detritum, Hyalomma marginatum marginatum and Rhipicephalus sanguineus. At least 31 different species of ticks from the genera Haemaphysalis and Hyalomma in southeastern Iran have been found to carry the virus. Wild animals and small mammals, particularly European hare, Middle-African hedgehogs and multimammate rats are the "amplifying hosts" of the virus. Birds are generally resistant to CCHF, with the exception of ostriches. Domestic animals like sheep, goats and cattle can develop high titers of virus in their blood, but tend not to fall ill. The "sporadic infection" of humans is usually caused by a Hyalomma tick bite. Animals can transmit the virus to humans, but this would usually be as part of a disease cluster. When clusters of illness occur, it is typically after people treat, butcher or eat infected livestock, particularly ruminants and ostriches. Outbreaks have occurred in abattoirs and other places where workers have been exposed to infected human or animal blood and fomites Humans can infect humans and outbreaks also occur in clinical facilities through infected blood and unclean medical instruments.
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