Generation of defective virus after infection of newborn rats with reovirus

Abstract

When 2 day old rats were inoculated s.c. with the R2 strain of reovirus type 3 or with a class B (352) or class C (447) temperature-sensitive (ts) mutant, 5-10% of the animals died from acute encephalitis within 12 days. Approximately half of the survivors recovered rapidly and grew normally, but the remainder became runted. Two phases of infection are distinguished in the animals: an acute phase during which infectious virus reaches a maximum titer in brain and other tissues by 10 days p.i. [post infection] and then rapidly decreases, and a succeeding chronic phase which involves runting of the rats and the slow disappearance of virus from their brains over a period of 2 mo. or so. Virus isolated from chronically infected brains generally retained the genetic character (ts or wild type) of the inoculated virus, but 2 exceptions to this are described. Defective virions lacking the L1 segment of the viral genome (L1 defectives) were generated in rat brains during the acute phase of infection. Defective virus was also generated during the chronic phase, but during this period defectives were found with multiple segments deleted from the genome in addition to L1 defectives. In another type of experiment defective virus exerted a marked protective effect when inoculated intracerebrally with R2 virus. In the absence of defectives all animals died, but in their presence 17 of 23 animals survived and 15 of 23 became runted and chronically infected. The formation and evolution of defective particles in the brains of these rats were similar to those found in rats chronically infected after subcutaneous inoculation of reovirus. The formation of defective virus particles may play a role in the initiation and maintenance of chronic neurotropic infections with reovirus.