Molecular Biology And Pathogenic Characteristics Of Hand,Foot And Mouth Disease Caused By Coxsackievirus A6 In Changchun Area

Hand-foot-mouth disease(HFMD)has erupted around the world since 2008,and a large-scale HFMD epidemic has been caused by CV-A6 in China in 2013.The current study of CV-A6 is only shown in case reports and epidemiological analysis,but its genetic characteristics and pathogenic characteristics have not been reported.In this study,we reported partial VP1 sequence of 39 CV-A6-Changchun strains(CV-A6-CC strain)isolated from patients with HFMD in Changchun area in 2013,and the whole genome sequence of four representative CV-A6-CC strains was obtained and register the Genbank database.The phylogenetic tree analysis of the VP1 region showed that the CV-A6-CC strain was distributed in three branches as CV-A6 from the rest of the world.The whole sequence of CV-A6-CC strain and CVA6 from the rest of the world were analyzed by phylogenetic tree,the results showed that CV-A6-CC strain might be derived from CV-A6 prototype strain Gdula and CVA6-Japan and Shanghai strains.According to the results of Bootscanning,CV-A6-Changchun strains may be recombinant strains of Gdula and CV-A4 or other CV-A4-like strains,the recombination pattern is not the same as CV-A6 isolates from other regions of China.Furthermore,we established a lethal neonatal ICR neonatal rat model,immunized mice with four virus strains,observed and recorded the clinical symptoms score and survival rate after immunization;in addition,we also determined the pathogenic neonatal tissue and the pathologic analysis was carried out to study the pathogenicity of CV-A6 virus to neonatal mice.The results showed that different CVA6-CC strain viruses had different pathogenicity in neonatal rat model,CV-A6-CC strain was divided into lethal strains(CC046,CC097 and CC099 strains)and nonlethal strains(CC098 strain)according to their pathogenic characteristics.Our study first reported that CV-A6 virus,which causes hand,foot and mouth disease,can be divided into lethal and non-lethal strains,which will lay the foundation for further study of the molecular mechanism of CV-A6 virus.