1887

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Volume 89, Issue 7

The molecular basis of mouse adaptation by human enterovirus 71 Free

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 virulence 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 K→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 (G→E) and the 2C protein (K→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 (K→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 (G→E) mutation alone was sufficient to increase virulence in mice to the level observed in MP-26M-infected mice.

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2008-07-01
2024-04-16
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The molecular basis of mouse adaptation by human enterovirus 71
J. Gen. Virol. 89, 1622 (2008); https://doi.org/10.1099/vir.0.83676-0
/content/journal/jgv/10.1099/vir.0.83676-0
/content/journal/jgv/10.1099/vir.0.83676-0
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