PROLONGED REPLICATION IN THE MOUSE CENTRAL-NERVOUS-SYSTEM OF REOVIRUSES ISOLATED FROM PERSISTENTLY INFECTED CELL-CULTURES

We examined pathogenic characteristics of plaque-purified reoviruses i solated from persistently infected L-cell cultures (PI viruses) after intracranial inoculation into newborn mice. The PI viruses were isolat ed from independent cultures initiated with high-passage stocks of the wild-type (wt) strain, type 3 Dearing. The virulence of most PI virus es was equivalent to that of the wt strain. However, replication of PI viruses in the central nervous system of infected mice was prolonged to 25 (but not 50) days postinoculation. Thirty-eight percent (n = 186 ) of mice inoculated with the PI viruses had residual virus detectable in brain tissue 25 days after inoculation, in contrast to only 16% (n = 57) of mice inoculated with wt virus (P = 0.009). Mean residual bra in titers were more than 20-fold higher in mice inoculated with PI vir uses compared with wt virus (4.3 x 10(4) versus 2.1 x 10(3) ; P = 0.00 6). Tropism of PI virus within the brain resembled that of wt virus, a nd the distribution of PI virus antigen in the brain did not change ov er time. The extent of necrosis in the brains of mice harboring PI vir us 25 days after inoculation was minimal, despite continued presence o f high titers of infectious virus. The latter observation resembles th e absence of cytopathicity seen in L-cell cultures persistently infect ed with reovirus. These observations suggest that the interaction of P I viruses with cells can be altered in vivo as well as in cell culture , but virus is eventually cleared from the infected animal.