Table 2.

Comparison of mouse and monkey neurovirulence following intracerebral inoculation, and amino acid differences between FNV-Yale and MRPR variants

VirusPFU/mouse LD50Mouse avg survival timeb (days ± SEM)Amino acid substitution (parent→variant)Monkey results
Actual survival time (days)Clinical scoreaHistology scorea
Discriminator areaDiscriminator plus target area
FNV-YALE0.085.4 ± 0.453.51.752.72
MKB MRPR I (pH 7.6)>100NAc E-260 (G→A)
MKB MRPR II (pH 7.6)326.5 ± 0.3E-274 (Y→H)63.41.522.49
MKB MRPR IV (pH 7.6)806.3 ± 0.3E-237 (H→Y)53.51.312.12
MKB MRPR (pH 6.0)77.2 ± 0.2d E-458 (G→R)
MS MRPR I (pH 7.6)57.6 ± 0.4d E-457 (M→I)
MS MRPR II (pH 7.6)87.2 ± 0.2d E-457 (M→I)
  • a The variants were indistinguishable from the parental virus on the basis of clinical score and histology score in either the discriminator areas or target plus discriminator areas, which are the usual criteria for evaluation of the World Health Organization neurovirulence test (12).

  • b ASTs were calculated based on an inoculum of 100 PFU given by the intracerebral route to 4-week-old female NIH Swiss mice.

  • c NA, not applicable.

  • d AST statistically longer than that of parental FNV-Yale virus, P < 0.2.