Crimean-Congo hemorrhagic fever (CCHF) is a severe illness with high fatality. Cases are reported in several countries in Africa, Europe, the Middle East, and Asia. Phylogenetic analyses based on the virus S (nucleocapsid), M (glycoprotein), and L (polymerase) genome segments sequences indicate distinct geographic lineages exist but their specific genetic characteristics require elucidation. In this work we collected all full length S segment sequences and generated a phylogenetic tree based on the alignment of these 62 samples. We then analyzed the alignment using entries from AAIndex, the Amino Acid Index database, to identify amino acid mutations that performed significant changes in charge, pka, hydropathy and side chain volume. Finally, we mapped these changes back to the tree and alignment to identify correlated mutations or sites that characterized a specific lineage. Based on this analysis we are able to propose a number of sites that appear to be important for virus function and which would be good candidates for experimental mutational analysis studies.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Albertini A A, Wernimont A K, Muziol T, et al. 2006. Crystal structure of the rabies virus nucleoprotein-RNA complex. Science, 313:360–363.
Anagnostou V, Papa A. 2009. Evolution of Crimean- Congo Hemorrhagic Fever virus. Infect Genet Evol, 9:948–954.
Aradaib I E, Erickson B R, Karsany M S, et al. 2011. Multiple crimean-congo hemorrhagic Fever virus strains are associated with disease outbreaks in Sudan, 2008–2009. PLoS Negl Trop Dis, 5:e1159.
Aradaib I E, Erickson B R, Mustafa M E, et al. 2010. Nosocomial outbreak of Crimean-Congo hemorrhagic fever, Sudan. Emerg Infect Dis, 16:837–839.
Chinikar S, Persson S M, Johansson M, et al. 2004. Genetic analysis of Crimean-congo hemorrhagic fever virus in Iran. J Med Virol, 73:404–411.
Drosten C, Minnak D, Emmerich P, et al. 2002. Crimean-Congo hemorrhagic fever in Kosovo. J Clin Microbiol, 40:1122–1123.
Eifan S A, Elliott R M. 2009. Mutational analysis of the Bunyamwera orthobunyavirus nucleocapsid protein gene. J Virol, 83:11307–11317.
Eisenberg D. 1984. Three-dimensional structure of membrane and surface proteins. Annu Rev Biochem, 53:595–623.
Elton D, Medcalf E, Bishop K, et al. 1999. Oligomerization of the influenza virus nucleoprotein: identification of positive and negative sequence elements. Virology, 260:190–200.
Elton D, Medcalf L, Bishop K, et al. 1999. Identification of amino acid residues of influenza virus nucleoprotein essential for RNA binding. J Virol, 73:7357–7367.
Fauchere J L, Charton M, Kier L B, et al. 1988. Amino acid side chain parameters for correlation studies in biology and pharmacology. Int J Pept Protein Res, 32:269–278.
Gao X, Nasci R, Liang G. 2010. The neglected arboviral infections in mainland China. PLoS Negl Trop Dis, 4:e624.
Gargili A, Midilli K, Ergonul O, et al. 2011. Crimean-congo hemorrhagic Fever in European part of Turkey: genetic analysis of the virus strains from ticks and a seroepidemiological study in humans. Vector Borne Zoonotic Dis, 11:747–752.
Goldsack D E, Chalifoux R C. 1973. Contribution of the free energy of mixing of hydrophobic side chains to the stability of the tertiary structure of proteins. J Theor Biol, 39:645–651.
Hewson R, Chamberlain J, Mioulet V, et al. 2004. Crimean-Congo haemorrhagic fever virus: sequence analysis of the small RNA segments from a collection of viruses world wide. Virus Res, 102:185–189.
Hoogstraal H. 1979. The epidemiology of tick-borne Crimean-Congo hemorrhagic fever in Asia, Europe, and Africa. J Med Entomol, 15:307–417.
Kawashima S, Pokarowski P, Pokarowska M, et al. 2008. AAindex: amino acid index database, progress report 2008. Nucl Acids Res, 36:D202–205.
Krigbaum W R, Komoriya A. 1979. Local interactions as a structure determinant for protein molecules: II. Biochim Biophys Acta, 576:204–248.
Kuhn J H, Seregin S V, Morzunov S P, et al. 2004. Genetic analysis of the M RNA segment of Crimean-Congo hemorrhagic fever virus strains involved in the recent outbreaks in Russia. Arch Virol, 149:2199–2213.
Longhi S. 2009. Nucleocapsid structure and function. Curr Top Microbiol Immunol, 329:103–128.
Meissner J D, Seregin S S, Seregin S V, et al. 2006. A variable region in the Crimean-Congo hemorrhagic fever virus L segment distinguishes between strains isolated from different geographic regions. J Med Virol, 78:223–228.
Midilli K, Gargili A, Ergonul O, et al. 2007. Imported Crimean-Congo hemorrhagic fever cases in Istanbul. BMC Infect Dis, 7:54.
Mild M, Simon M, Albert J, et al. 2010. Towards an understanding of the migration of Crimean-Congo hemorrhagic fever virus. J Gen Virol, 91:199–207.
Mir M A, Panganiban A T. 2005. The hantavirus nucleocapsid protein recognizes specific features of the viral RNA panhandle and is altered in conformation upon RNA binding. J Virol, 79:1824–1835.
Mohl B P, Barr J N. 2009. Investigating the specificity and stoichiometry of RNA binding by the nucleocapsid protein of Bunyamwera virus. RNA, 15:391–399.
Papa A, Velo E, Papadimitriou E, et al. 2009. Ecology of the Crimean-Congo hemorrhagic fever endemic area in Albania. Vector Borne Zoonotic Dis, 9:713–716.
Roseman M A. 1988. Hydrophilicity of polar amino acid side-chains is markedly reduced by flanking peptide bonds. J Mol Biol, 200:513–522.
Sun S, Dai X, Aishan M, et al. 2009. Epidemiology and phylogenetic analysis of crimean-congo hemorrhagic fever viruses in xinjiang, china. J Clin Microbiol, 47:2536–2543.
Tahmasebi F, Ghiasi S M, Mostafavi E, et al. 2010. Molecular epidemiology of Crimean- Congo hemorrhagic fever virus genome isolated from ticks of Hamadan province of Iran. J Vector Borne Dis, 47:211–216.
Tamura K, Peterson D, Peterson N, et al. 2011. MEGA5: Molecular Evolutionary Genetics Analysis using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods. Mol Biol Evol. 2011 May 4. [Epub ahead of print].
Terribilini M, Lee J H, Yan C, et al. 2006. Prediction of RNA binding sites in proteins from amino acid sequence. RNA, 12:1450–1462.
Thompson J D, Higgins D G, Gibson T J. 1994. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucl Acids Res, 22:4673–4680.
Tonbak S, Aktas M, Altay K, et al. 2006. Crimean-Congo hemorrhagic fever virus: genetic analysis and tick survey in Turkey. J Clin Microbiol, 44:4120–4124.
Tsai J, Taylor R, Chothia C, et al. 1999. The packing density in proteins: standard radii and volumes. J Mol Biol, 290:253–266.
Walter C T, Bento D F, Alonso A G, et al. 2011. Amino acid changes within the Bunyamwera virus nucleocapsid protein differentially affect the mRNA transcription and RNA replication activities of assembled ribonucleoprotein templates. J Gen Virol, 92:80–84.
Xia H, Li P, Yang J, et al. 2011. Epidemiological survey of Crimean-Congo hemorrhagic fever virus in Yunnan, China, 2008. Int J Infect Dis, 15:e459–463.
Yashina L, Vyshemirskii O, Seregin S, et al. 2003. Genetic analysis of Crimean-Congo hemorrhagic fever virus in Russia. J Clin Microbiol, 41:860–862.
Ye Q, Krug R M, Tao Y J. 2006. The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNA. Nature, 444:1078–1082.
Rights and permissions
About this article
Cite this article
Han, N., Rayner, S. Epidemiology and mutational analysis of global strains of crimean-congo haemorrhagic fever virus. Virol. Sin. 26, 229–244 (2011). https://doi.org/10.1007/s12250-011-3211-z
- Crimean-Congo hemorrhagic fever virus (CCHFV)
- Mutational Analysis