Recovery of West Nile virus envelope protein domain III chimeras with altered antigenicity and mouse virulence

Alexander J. McAuley, Maricela Torres, Jessica Plante, Claire Y H Huang, Dennis Bente, David Beasley

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Flaviviruses are positive-sense, single-stranded RNA viruses responsible for millions of human infections annually. The envelope (E) protein of flaviviruses comprises three structural domains, of which domain III (EIII) represents a discrete subunit. The EIII gene sequence typically encodes epitopes recognized by virus-specific, potently neutralizing antibodies, and EIII is believed to play a major role in receptor binding. In order to assess potential interactions between EIII and the remainder of the E protein and to assess the effects of EIII sequence substitutions on the antigenicity, growth, and virulence of a representative flavivirus, chimeric viruses were generated using the West Nile virus (WNV) infectious clone, into which EIIIs from nine flaviviruses with various levels of genetic diversity from WNV were substituted. Of the constructs tested, chimeras containing EIIIs from Koutango virus (KOUV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV), and Bagaza virus (BAGV) were successfully recovered. Characterization of the chimeras in vitro and in vivo revealed differences in growth and virulence between the viruses, with in vivo pathogenesis often not being correlated with in vitro growth. Taken together, the data demonstrate that substitutions of EIII can allow the generation of viable chimeric viruses with significantly altered antigenicity and virulence.

Original languageEnglish (US)
Pages (from-to)4757-4770
Number of pages14
JournalJournal of Virology
Volume90
Issue number9
DOIs
StatePublished - May 1 2016

ASJC Scopus subject areas

  • Immunology
  • Virology

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