The variability of the large genomic segment of Ťahyňa orthobunyavirus and an all-atom exploration of its anti-viral drug resistance
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24090866
DOI
10.1016/j.meegid.2013.09.023
PII: S1567-1348(13)00364-X
Knihovny.cz E-resources
- Keywords
- 2,4-dioxo-4-phenylbutanoic acid, AKAV, Akabane virus, BUNV, Bunyamwera virus, CAL, CHATV, California complex, Chatanga virus, DPBA, ED, Genetic variability, INKV, Inkoo virus, L, LACV, La Crosse virus, Large genomic segment, M, ML, MP, N, NSs, ORF, OROV, OTU-like, Orthobunyavirus, PELE, RMSD, S, TAHV, VF, d(N), d(S), endonuclease domain, large genomic segment, maximum likelihood, maximum parsimony, medium genomic segment, non-synonymous nucleotide substitution rate, nonstructural protein encoded by S segment, nucleocapsid protein, open reading frame, oropouche virus, ovarian tumour-like, protein energy landscape exploration, root mean square deviation, small genomic segment, synonymous nucleotide substitution rate, temperature-sensitive, ts, valtice fever, Ťahyňa virus,
- MeSH
- Antiviral Agents pharmacology MeSH
- Phylogeny MeSH
- Genetic Variation MeSH
- Genome, Viral genetics MeSH
- Genotype MeSH
- Humans MeSH
- Molecular Sequence Data MeSH
- RNA, Viral genetics MeSH
- Amino Acid Sequence MeSH
- Base Sequence MeSH
- Sequence Analysis, DNA MeSH
- Sequence Alignment MeSH
- Drug Resistance, Viral genetics MeSH
- Viral Proteins genetics MeSH
- Encephalitis Virus, California drug effects genetics isolation & purification MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antiviral Agents MeSH
- L protein, Bunyamwera virus MeSH Browser
- RNA, Viral MeSH
- Viral Proteins MeSH
Ťahyňa virus (TAHV), a member of the Bunyaviridae family (California complex), is an important but neglected human mosquito-borne pathogen. The virus genome is composed of three segments, i.e., small (S), medium (M), and large (L). Previous studies on genetic variability of viruses within the California complex were focused on S and M segments, but the L segment remains relatively unstudied. To assess the genetic variation and the relation to virus phenotype we analyzed the L segment sequences of biologically diverse TAHV strains isolated in the Czech Republic and Slovakia. Phylogenetic analysis covering all available sequences of the L segment of TAHV clearly revealed two distinguished lineages, tentatively named as "European" and "Asian". The L segment strains within the European lineage are highly conserved (identity 99.3%), whilst Asian strains are more genetically diverse (identity 97%). Based on sequence comparison with other bunyaviruses, several non-synonymous nucleotide substitutions unique for TAHV in the L segment were identified. We also identified specific residue substitutions in the endonuclease domain of TAHV compared with the La Crosse virus. Since the endonuclease domain of the La Crosse virus has been resolved, we employed an all energy landscape algorithm to analyze the ligand migration of a viral polymerase inhibitor. This allowed us to demonstrate, at the atomic level, that this viral polymerase inhibitor randomly explored the specific residue substitutions in the endonuclease domain of the TAHV L segment.
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