Synonymous codon bias in the viral genome affects protein translation and gene expression, suggesting that the synonymous codon mutant plays an essential role in influencing virulence and evolution. However, how the recessive mutant form contributes to virus evolvability remains elusive. In this paper, we characterize how the Senecavirus A (SVA), a picornavirus, utilizes synonymous codon mutations to influence its evolution, resulting in the adaptive evolution of the virus to adverse environments. The phylogenetic tree and Median-joining (MJ)-Network of these SVA lineages worldwide were constructed to reveal SVA three-stage genetic development clusters. Furthermore, we analyzed the codon bias of the SVA genome of selected strains and found that SVA could increase the GC content of the third base of some amino acid synonymous codons to enhance the viral RNA adaptive evolution. Our results highlight the impact of recessive mutation of virus codon bias on the evolution of the SVA and uncover a previously underappreciated evolutionary strategy for SVA. They also underline the importance of understanding the genetic evolution of SVA and how SVA adapts to the adverse effects of external stress.
Background Senecavirus A (SVA), a member of the family Picornaviridae , is newly discovered, which causes vesicular lesions, lameness in swine, and even death in neonatal piglets. SVA has rapidly spread worldwide in recent years, especially in Asia. Objectives We conducted a global meta-analysis and systematic review to determine the status of SVA infection in pigs. Methods Through PubMed, VIP Chinese Journals Database, China National Knowledge Infrastructure, and Wanfang Data search data from 2014 to July 26, 2020, a total of 34 articles were included in this analysis based on our inclusion criteria. We estimated the pooled prevalence of SVA in pigs by the random effects model. A risk of bias assessment of the studies and subgroup analysis to explain heterogeneity was undertaken. Results We estimated the SVA prevalence to be 15.90% (1,564/9,839; 95% confidence interval [CI], 44.75–65.89) globally. The prevalence decreased to 11.06% (945/8,542; 95% CI, 28.25–50.64) after 2016. The highest SVA prevalence with the VP1-based RT-PCR and immunohistochemistry assay was 58.52% (594/1,015; 95% CI, 59.90–83.96) and 85.54% (71/83; 95% CI, 76.68–100.00), respectively. Besides, the SVA prevalence in piglet herds was the highest at 71.69% (119/166; 95% CI, 68.61–98.43) ( p < 0.05). Moreover, our analysis confirmed that the subgroups, including country, sampling year, sampling position, detected gene, detection method, season, age, and climate, could be the heterogeneous factors associated with SVA prevalence. Conclusions The results indicated that SVA widely exists in various countries currently. Therefore, more prevention and control policies should be proposed to enhance the management of pig farms and improve breeding conditions and the environment to reduce the spread of SVA.
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