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Genomic characterization of coxsackievirus type A24 strains associated with acute flaccid paralysis and rarely identified Hopkins syndrome

Abstract

The full-length genome sequence analysis of four coxsackievirus A24 (CV-A24) strains, detected in three paralytic and one post-asthmatic paralytic (Hopkins syndrome) cases, is reported here for the first time. A phylogenetic tree constructed on the basis of entire genomes displayed topology similar to that of the full-VP1 tree, classifying the study strains in genogroup CV-A24vGIV along with their temporal counterparts in strains from non-paralytic cases. The strains of the study formed a single genetic cluster C4 within CV-A24vGIV and showed 3.5–19.4 % nucleotide sequence divergence, with 2-4 novel nucleotide mutations in the 5′NCR and 3-8 unique amino acid substitutions in the polyprotein, with respect to the CV-A24 strains associated with non-paralytic cases. Among the nucleotide mutations, A299U was identified in the 5′NCRs of all of the study strains. CV-A24v strains of the same genogroup with few genomic variations but different disease manifestations need to be explored to investigate the molecular basis of evolution of neurovirulence.

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Acknowledgments

The authors thank the Indian Council of Medical Research, New Delhi, for supporting the first author (RL) with a research fellowship, Dr. D.T. Mourya, Director, NIV, Pune, for constant support during this study, Mr. Atul M. Walimbe for discussions on phylogenetic analysis, and Dr. Sarah Cherian for help in revising the manuscript. The authors also thank the entire team of personnel involved in the network of Polio Surveillance, India, especially all of the technical Staff of National Polio Laboratory, Bangalore, for providing data on AFP cases.

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Correspondence to Shobha D. Chitambar.

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Fig. S1

Phylogenetic tree constructed on the basis of the 3C (nt 5460–6009) nucleotide sequences of CV-A24 strains using the neighbor-joining method and maximum composite likelihood model with 1000 bootstrap replications. ■ denotes strains from AFP cases of the present study, ▲ denotes strains from non-AFP cases from India and △ denotes strains from non-AFP cases from other countries.(TIFF 852 kb)

Fig. S2.

Venn diagram indicating the distribution of the novel mutations (nt / aa) detected in the 5′ NCR and polyprotein sequences of the study strains, identified by blastn or tblastn algorithms available on the NCBI website. The mutations are numbered with respect to the prototype Joseph strain (GenBank accession no. EF026081). Radical amino acid substitutions are underlined.(TIFF 3201 kb)

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Laxmivandana, R., Yergolkar, P., Rajeshwari, M. et al. Genomic characterization of coxsackievirus type A24 strains associated with acute flaccid paralysis and rarely identified Hopkins syndrome. Arch Virol 159, 3125–3129 (2014). https://doi.org/10.1007/s00705-014-2129-9

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Keywords

  • Internal Ribosome Entry Site
  • Acute Flaccid Paralysis
  • Nucleotide Mutation
  • Amino Acid Sequence Diversity
  • Study Strain