A single amino acid substitution in the murine norovirus capsid protein is sufficient for attenuation in vivo.
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.
Bailey
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D
Department of Virology, Faculty of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom.
Thackray
L B
LB
Goodfellow
I G
IG
D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D017250:Caliciviridae Infections / Q000821:virology*; D036022:Capsid Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D051379:Mice; D018345:Mice, Knockout; D029322:Norovirus / Q000235:genetics* / Q000472:pathogenicity*; D050791:STAT Transcription Factors / Q000172:deficiency; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D014774:Virulence
D036022:Capsid Proteins; D050791:STAT Transcription Factors