The molecular basis of mouse adaptation by human enterovirus 71

B.H. Chua; P. Phuektes; S.A. Sanders; P.K. Nicholls; P.C. McMinn

doi:10.1099/vir.0.83676-0

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The molecular basis of mouse adaptation by human enterovirus 71

Journal article

Open access

Peer reviewed

The molecular basis of mouse adaptation by human enterovirus 71

B.H. Chua, P. Phuektes, S.A. Sanders, P.K. Nicholls and P.C. McMinn

Journal of General Virology, Vol.89(7), pp.1622-1632

2008

DOI: https://doi.org/10.1099/vir.0.83676-0

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Abstract

A mouse-adapted strain of human enterovirus 71 (HEV71) was selected by serial passage of a HEV71 clinical isolate (HEV71-26M) in Chinese hamster ovary (CHO) cells (CHO-26M) and in newborn BALB/c mice (MP-26M). Despite improved growth in CHO cells, CHO-26M did not show increased vilrulence in newborn BALB/c mice compared with HEV71-26M. By contrast, infection of newborn mice with MP-26M resulted in severe disease of high mortality. Skeletal muscle was the primary site of replication in mice for both viruses. However, MP-26M infection induced severe necrotizing myositis, whereas CHO-26M infection caused only mild inflammation. MP-26M was also isolated from whole blood, heart, liver, spleen and brain of infected mice. CHO-26M harboured a single mutation within the open reading frame (ORF), resulting in an amino acid substitution of K149-I in the VP2 capsid protein; two further ORF mutations that resulted in amino acid substitutions were identified in MP-26M, located within the VP1 capsid protein (G145-E) and the 2C protein (K216-R). Infectious cDNA clone-derived mutant virus populations containing the mutations identified in CHO-26M and MP-26M were generated in order to study the molecular basis of CHO cell and mouse adaptation. The VP2 (K149-I) change was responsible only for improved growth in CHO cells and did not lead to increased virulence in mice. Of the two amino acid substitutions identified in MP-26M, the VP1 (G145-E) mutation alone was sufficient to increase virulence in mice to the level observed in MP-26M-infected mice.

Details

Title: The molecular basis of mouse adaptation by human enterovirus 71
Authors/Creators: B.H. Chua (Author/Creator) - The Kids Research Institute Australia
P. Phuektes (Author/Creator) - Murdoch University
S.A. Sanders (Author/Creator) - The Kids Research Institute Australia
P.K. Nicholls (Author/Creator) - Murdoch University
P.C. McMinn (Author/Creator) - The University of Sydney
Publication Details: Journal of General Virology, Vol.89(7), pp.1622-1632
Publisher: Society for General Microbiology
Identifiers: 991005542869107891
Copyright: © 2008 SGM.
Murdoch Affiliation: School of Veterinary and Biomedical Sciences
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.104 Virology - General; 1.104.901 Enterovirus Research
Web Of Science research areas: Biotechnology & Applied Microbiology; Virology
ESI research areas: Microbiology