SEQUENTIAL DISTRIBUTION OF NEUROVIRULENT AND AVIRULENT STRAINS OF BLUETONGUE VIRUS IN NEONATAL MICE BY RT-PCR

Neurotropism of bluetongue virus (BLU) has been demonstrated in the de veloping brain of fetal ruminants and neonatal mouse models. Two strai ns of BLU serotype 11, UC8 and UC2, differentiated by their electropho retic characteristics and abilities to cause brain lesions in bovine f etuses and neonatal mice were investigated to determine differences in tissue distribution in new born mice following subcutaneous inoculati on. Tissue analysis by reverse transcriptase-polymerase chain reaction (RT-PCR) showed selective distribution of both BLU strains to the bra in and spleen as early as 3 h post-inoculation (PI) but viral RNA was not detected in the blood or other tissues for the duration of the 15 day experiment. UC2 persisted within the brain and spleen until 9 h PI without development of CNS lesions. In contrast, UC8 persisted within the spleen for 24 h and in the brain through the end of the experimen t. UC8 infected mice developed necrotizing lesions throughout the cere brum and cerebellum that were most severe on PI days 11 and 13. Immuno histochemical staining for BLU identified infected cells within the br ains of UC8 inoculated mice before inflammatory lesions were present a nd gave supportive evidence of the ability of UC2 to infect brain cell s. Our results show that both UC8 and UC2 selectively target the brain and spleen in neonatal mice early after inoculation and suggest that the differences in neurovirulence between these strains are due to dif ferences in replicative efficacy within host target cells.