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ABSTRACT: Using the complete genome sequences of 35 classical swine fever viruses (CSFV) representing all three genotypes and all three kinds of virulence, we analyzed synonymous codon usage and the relative dinucleotide abundance in CSFV. The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in CSFV. Furthermore, we observed that the relative abundance of dinucleotides in CSFV is independent of the overall base composition but is still the result of differential mutational pressure, which also shapes codon usage. In addition, other factors, such as the subgenotypes and aromaticity, also influence the codon usage variation among the genomes of CSFV. This study represents the most comprehensive analysis to date of CSFV codon usage patterns and provides a basic understanding of the mechanisms for codon usage bias.
Virus Genes 11/2008; 38(1):104-12. · 1.85 Impact Factor
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Yi Wang,
Qin Wang,
Xiaolu Lu,
Chuyu Zhang,
Xuezheng Fan,
Zishu Pan,
Lu Xu,
Guoyuan Wen,
Yibao Ning, Fangqiang Tang,
Yanhua Xia
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ABSTRACT: We report here the discovery of an attenuation mechanism of classic swine fever virus (CSFV) induced by introduction of a continuous 12-nt (CUUUUUUCUUUU) insertion in viral 3' UTR. The 12-nt insertion sequence was first found in one attenuated vaccine strain HCLV (Hog Cholera Lapinized Virus) which did not exist in other CSFV strains. To address the function of the 12-nt insertion in viral replication and attenuation, we constructed and analyzed two chimeras stemmed from a highly virulent strain Shimen either with introduction of the 12-nt insertion in 3' UTR or the replacement of viral 3' UTR by the 3' UTR of HCLV. We found that the two chimeras' maximum titers declined approximately 100-fold than their parental strain Shimen in PK15 cells. An animal experiment showed that the two chimeras were both dramatically attenuated in pigs. All the chimera-infected pigs survived infection and remained clinically normal with the exception of a transient fever while the 100% mortality was observed for the Shimen-infected pigs. In addition, the two chimeras can induce neutralization antibody to completely protect the pigs against lethal challenge with highly virulent CSFV, which was similar to the vaccine strain HCLV. These data demonstrate that the 12-nt insertion in 3' UTR is sufficient for the attenuation of CSFV. Taken together, a novel attenuation mechanism of CSFV is found and may pave a way to further research for new attenuated vaccine.
Virology 06/2008; 374(2):390-8. · 3.35 Impact Factor
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ABSTRACT: Classical swine fever virus, one member of the family Flaviviridae, is the pathogen of CSF, an economically important and highly contagious disease of pigs. Knowledge of virus genes under positive selection pressure can help identify molecular determinants of virulence or pathogenesis without prior knowledge of the mechanisms governing virulence and pathogenesis and clarify the driving force of classical swine fever virus evolution. The positive selection pressure acting on envelope protein genes E(rns), E1 and E2 of classical swine fever virus were assessed and a site-by-site analysis of the d(N)/d(S) ratio was performed, to identify specific codons undergoing diversifying positive selection. Whilst no significant evidence for positive selection was observed in E1, four positively selected sites (208 in E(rns) and 72, 75, and 200 in E2) were identified. The positively selected site (208) of E(rns) corresponds to one of the amino acid substitutions (Ser to Arg) found in an HS-binding CSFV variant. The mutant at the positively selected site (75) is located within an O-glycosylation motif and altered the predicted glycosylation pattern. In addition, Thr at the positively selective site 200 are directly involved with mAb WH308 with which CS vaccine strain does not react, unlike most of the virulent CSFV strains.
Virus Research 03/2008; 131(2):132-5. · 2.94 Impact Factor
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ABSTRACT: Despite the growing interest in the molecular epidemiology of pestivirus, there have been few attempts to determine which regions of the pestivirus genome are subject to positive selection, although this may be a key indicator of the nature of the interaction between host and virus. By using likelihood-based methods for phylogenetic inference, the positive selection pressure of BVDV-1 E2 gene were assessed and a site-by-site analysis of the dN/dS ratio was performed, to identify specific codons undergoing diversifying positive selection. The overall omega was 0.20, indicating that most sites were subject to strong purifying selection and five positively selected sites (886, 888, 905, 944, and 946) were identified. It is surprising to find that all the potential positively selected sites fall within the C-terminal of E2, and out of the N-terminal of E2 which is thought to be surface-exposed and therefore prime targets for host antibody response. In conclusion, these results suggest that selection favoring avoidance of antibody recognition has not been a major factor in the history of BVDV-1. Further analysis is necessary to see if amino acid substitutions in the BVDV-1 positively selected sites can lead to change of host tropism or\and escape from epitope-specific CD8 T-cell response.
Virus Genes 01/2008; 35(3):629-34. · 1.85 Impact Factor
