Next generation sequencing of human enterovirus strains from an outbreak of enterovirus A71 shows applicability to outbreak investigations

Sacha Stelzer-Braid, Matthew Wynn, Richard Chatoor, Matthew Scotch, Vidiya Ramachandran, Hooi Ling Teoh, Michelle A. Farrar, Hugo Sampaio, Peter Ian Andrews, Maria E. Craig, C. Raina MacIntyre, Hemalatha Varadhan, Alison Kesson, Philip N. Britton, James Newcombe, William D. Rawlinson

Research output: Contribution to journalArticle

Abstract

Background: The most recent documented Australian outbreak of enterovirus A71 (EV-A71) occurred in Sydney from 2012 to 2013. Over a four-month period more than 100 children presented to four paediatric hospitals with encephalitic presentations including fever and myoclonic jerks. The heterogeneous presentations included typical encephalomyelitis, and cardiopulmonary complications. Objectives: To characterise the genomes of enterovirus strains circulating during the 2013 Sydney EV-A71 outbreak and determine their phylogeny, phylogeography and association between genome and clinical phenotype. Study design: We performed an analysis of enterovirus (EV) positive specimens from children presenting to hospitals in the greater Sydney region of Australia during the 2013 outbreak. We amplified near full-length genomes of EV, and used next generation sequencing technology to sequence the virus. We used phylogenetic/phylogeographic analysis to characterize the outbreak viruses. Results: We amplified and sequenced 23/63 (37 %) genomes, and identified the majority (61 %) as EV-A71. The EV-A71 sequences showed high level sequence homology to C4a genogroups of EV-A71 circulating in China and Vietnam during 2012-13. Phylogenetic analysis showed EV-A71 strains associated with more severe symptoms, including encephalitis or cardiopulmonary failure, grouped together more closely than those from patients with hand, foot and mouth disease. Amongst the non-EV-A71 sequences were five other EV subtypes (representing enterovirus subtypes A and B), reflecting the diversity of EV co-circulation within the community. Conclusions: This is the first Australian study investigating the near full-length genome of EV strains identified during a known outbreak of EV-A71. EV-A71 sequences were very similar to strains circulating in Asia during the same time period. Whole genome sequencing offers additional information over routine diagnostic testing such as characterisation of emerging recombinant strains and inform vaccine design.

Original languageEnglish (US)
Article number104216
JournalJournal of Clinical Virology
Volume122
DOIs
StatePublished - Jan 2020

Keywords

  • Australia
  • EV-A71
  • Enterovirus
  • Hand, foot and mouth disease
  • Phylogeny
  • Whole genome sequencing

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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    Stelzer-Braid, S., Wynn, M., Chatoor, R., Scotch, M., Ramachandran, V., Teoh, H. L., Farrar, M. A., Sampaio, H., Andrews, P. I., Craig, M. E., MacIntyre, C. R., Varadhan, H., Kesson, A., Britton, P. N., Newcombe, J., & Rawlinson, W. D. (2020). Next generation sequencing of human enterovirus strains from an outbreak of enterovirus A71 shows applicability to outbreak investigations. Journal of Clinical Virology, 122, [104216]. https://doi.org/10.1016/j.jcv.2019.104216