Differences between C57BL/6 and BALB/cBy mice in mortality and virus replication after intranasal infection with neuroadapted Sindbis virus

Neuroadapted Sindbis virus (NSV), given intranasally, caused fatal encephal itis in 100% of adult C57BL/6 mice and 0% of BALB/cBy mice. Most C57BL/6 mi ce developed severe kyphoscoliosis followed by hind-limb paralysis, while B ALB/cBy mice did not. In situ hybridization for detecting NSV RNA and immun ohistochemistry for detecting NSV antigen indicated that virus delivered by this route infected neurons of the olfactory region and spread caudally wi thout infection of ependymal cells. Virus antigen was more abundant and inf ectious virus increased more rapidly and reached higher levels in C57BL/6 m ice than in BALB/cBy mice. Surprisingly, infectious virus was cleared faste r in C57BL/6 mice, and this was associated with more rapid production of ne utralizing antibody. However, viral RNA was cleared more slowly in C57BL/6 mice. In both mouse strains, more infectious virus was present in the lumba r spinal cord than in the cervical spinal cord. These data suggest that gen etic susceptibility to fatal NSV encephalomyelitis is determined at least T n part by the efficiency of viral replication and spread in the central ner vous system. The differences identified in this study provide possible phen otypes for mapping genetic loci involved in susceptibility.