Single amino acid substitution in the murine norovirus capsid protein is sufficient for attenuation in vivo

被引:51
作者
Bailey, D. [1 ]
Thackray, L. B. [2 ]
Goodfellow, I. G. [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Dept Virol, Fac Med, London W2 1PG, England
[2] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA
基金
英国惠康基金;
关键词
D O I
10.1128/JVI.00237-08
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Murine norovirus (MNV), a prevalent pathogen of laboratory mice, shares many characteristics with human noroviruses. Previous results indicated that passage of MNV1 in the macrophage cell line RAW 264.7 results in attenuation in STAT1-deficient mice (C. E. Wobus, S. M. Karst, L. B. Thackray, K. O. Chang, S. V. Sosnovtsev, G. Belliot, A. Krug, J. M. Mackenzie, K. Y. Green, and H. W. Virgin, PLoS. Biol. 2:e432, 2004). Sequence analysis revealed two amino acid differences between the virulent and attenuated viruses. Using an infectious cDNA clone of the attenuated virus, we demonstrated that a glutamate-to-lysine substitution at position 296 in the capsid protein (VP1) is sufficient to restore virulence in vivo, identifying, for the first time, a virus-encoded molecular determinant of norovirus virulence.
引用
收藏
页码:7725 / 7728
页数:4
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