Immune Cell Tropisms of Attenuated MHV3 Viruses Isolated from Brains of Chronically Infected Mice

Isolation of infectious viruses from the brain during a chronic neurological disease is infrequent because persistent viruses differ from the parental virus in their virulence and in the development in genomic or replication defects. We have isolated mouse hepatitis virus 3 (MHV3) variants from the brain of chronically infected mice up to 105 days postinfection by culture on overconfluent L2 cells. In spite of atrophy and leukopenia observed in lymphoid organs of these mice, no viruses were isolated in numerous attempts. In contrast, defective-interfering viruses were detected in peritoneal exudate cells from chronically-infected mice. Brain-derived viruses differ from parental virus in their delayed fusion activity and attenuated pathogenicity for C57BL/6 and A/J mice. The attenuated brain isolates have ceased to replicate in thymocytes but replicated in nonadherent spleen and peritoneal exudate cells.