Abstract
Enterovirus, like the majority of RNA viruses, evolves to survive the changeable environments by a variety of strategies. Here, we showed that HY12 virus evolved to alter its characteristics and pathogenicity by employing a non-synonymous mutation. Analyses of 5′UTR, VP1 and VP2 gene sequences revealed the existence of HY12 virus in an array of mutants defined as quasispecies. The determination of diversity and complexity showed that the mutation rate and complexity of HY12 virus quasispecies increased, while the proportion of HY12 VP1 and VP2 consensus (master) sequences decreased with increasing passages. Synonymous mutation and non-synonymous mutation analysis displayed a positive selection for HY12 quasispecies evolution. A comparison of HY12 virus in different passages demonstrated that HY12 virus altered its characteristic, phenotype, and pathogenicity via non-synonymous mutation. These findings revealed the evolution pattern for HY12 virus, and the alteration of HY12 virus characteristics and pathogenicity by mutation.
Highlights
Virus uses different strategies to survive the changeable environments
Similar to other bovine enteroviruses (BEV), the complete genome sequence of EV-E HY12 strain is composed of 7469 nucleotides, where it contains one open reading frame (ORF) encoding a polyprotein of 2176 aa, a 5 -UTR consisting of 817 nucleotides, and 3 -UTR containing 68 nucleotides followed by a poly (A) tail with 53 polyadenines
We found that HY12 enterovirus exists as an array of closely related mutants, revealed the evolution pattern of quasispecies, and demonstrated that HY12 virus alters its phenotype, characteristics, and pathogenicity via non-synonymous mutation, likely affecting the outcome of clinical modes
Summary
Virus uses different strategies to survive the changeable environments. Enterovirus, like the majority of RNA viruses, employs the strategies of mutation to adapt the surroundings and implicate in pathogenesis [1,2,3,4]. Virus quasispecies refers to a virus population composed of a series of virus mutants with similar but different gene sequences These mutants continue to experience genetic mutation, competition, and selection in response to a variety of external factors, which is the driving force for virus evolution. We used the HY12 virus as a model to determine the evolution pattern of virus virulence and quasispecies in an attempt to address our hypothesis that the mutation of enterovirus leads to virus virulence alteration by analyzing viral structural protein VP1 and VP2 sequence from different passages. We found that HY12 enterovirus exists as an array of closely related mutants, revealed the evolution pattern of quasispecies, and demonstrated that HY12 virus alters its phenotype, characteristics, and pathogenicity via non-synonymous mutation, likely affecting the outcome of clinical modes
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