Mutations in VP2 and VP1 capsid proteins increase infectivity and mouse lethality of enterovirus 71 by virus binding and RNA accumulation enhancement

Sheng Wen Huang, Ya Fang Wang, Chun Keung Yu, Ih Jen Su, Jen Ren Wang

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Enterovirus 71 (EV71) is a major cause of hand-foot-and-mouth disease. EV71 infection occasionally associates with severe neurological sequelae such as brainstem encephalitis or poliovirus-like paralysis. We demonstrated that mouse-adapted strain increases infectivity, resulting in higher cytotoxicity of neuron cells and mortality to neonatal mice than a non-adapted strain. Results pointed to EV71 capsid region determining viral infectivity and mouse lethality. Mutant virus with lysine to methionine substitution at VP2 149 (VP2 149M) or glutamine to glutamic acid substitution at VP1 145 (VP1 145E) showed greater viral titers and apoptosis. Synergistic effect of VP2 149M and VP1 145E double mutations enhanced viral binding and RNA accumulation in infected Neuro-2a cells. The dual substitution mutants markedly reduced value of 50% lethal dose in neonatal mice infection, indicating they raised mouse lethality in vivo. In sum, VP2 149M and VP1 145E mutations cooperatively promote viral binding and RNA accumulation of EV71, contributing to viral infectivity in vitro and mouse lethality in vivo.

Original languageEnglish
Pages (from-to)132-143
Number of pages12
JournalVirology
Volume422
Issue number1
DOIs
Publication statusPublished - 2012 Jan 5

All Science Journal Classification (ASJC) codes

  • Virology

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