Abstract:To analyze the epidemiology, genetic variation and genetic evolution of coxsackievirus A4 (CVA4) in patients with hand, foot and mouth disease in Fujian, the virus isolates were molecular typed and amplified the whole VP1 region by RT-PCR, then the genetic variation and evolution were studied. The results showed that 33 CVA4 cases (8.1%) were confirmed from the 407 non-EV71 non-CVA16 HFMD cases in Fujian Province during 2011 and 2014, accounting for 31 cases in 2012 and 2 cases in 2014. Compared with common characteristics of the HFMD epidemic, no specificity in the distribution of CVA4 cases was found between gender and age groups. Sequence analysis of VP1 nucleotide sequences of Fujian CVA4 isolates showed that the nucleotide and amino acid sequences similarity were 92.6%-100% and 95.7%-100% respectively, low similarity with the prototype (83.7%-85.4%, 96.1%-99.0%) and abroad isolates (82.1%-89.1%, 90.4%-99.6%) both in nucleotide and amino acid sequences, high similarity with domestic isolates both in nucleotide and amino acid sequences, with the similarity of 87.9%-99.2% and 96.1%-100%. The results from phylogenetic tree showed that the genetic distance between Fujian CVA4 isolates and the prototype and abroad strains was far, and the genetic distance was close to domestic isolates in China. The distribution of the phylogenetic trees of Fujian CVA4 strains showed multiple branches. Therefore, CVA4 is the major HFMD associated-pathogen other than EV71, CVA16, CVA6, and CVA10 in Fujian Province from 2011 to 2014. CVA4 strains from Fujian Province is co-circulating and co-evolving with other domestic isolates. There is existence of multiple closely related CVA4 transmission chains in various regions of Fujian.
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