MOLECULAR CHARACTERIZATION OF VIRUS-SPECIFIC RNA PRODUCED IN THE BRAINS OF FLAVIVIRUS-SUSCEPTIBLE AND FLAVIVIRUS-RESISTANT MICE AFTER CHALLENGE WITH MURRAY VALLEY ENCEPHALITIS-VIRUS

Natural resistance to flaviviruses in mice is controlled by a single g enetic locus, Flv, on chromosome 5. Although the mechanism of this res istance is not fully understood, it is believed to operate at the leve l of virus replication rather than the immune response. It has been hy pothesized that enhanced production of viral defective interfering (DI ) particles is responsible for a substantial reduction in the titres o f infectious virus in resistant mice, However, this has never been est ablished at the molecular level since such particles have not been iso lated and characterized, We have studied the products of virus replica tion in the brains of flavivirus-susceptible C3H/HeJ (Flv(s)) and -res istant congenic C3H/RV (Flv(r)) mice after an intracerebral challenge (i.c.) with Murray Valley encephalitis (MVE) virus and have found no e vidence for the accumulation of truncated viral RNA in the brains of r esistant mice. All three major viral RNA species, the replicative inte rmediate (RI), replicative form (RF) and virion RNA (vRNA) together wi th a subgenomic RNA species of 0 . 6 kb, which has not been previously described, were present in the brains of both mouse strains. However, the viral RF and RI RNA forms preferentially accumulated in the brain s of resistant mice. Thus, we confirm that the resistance allele Flv(r ) interferes with discrete steps in flavivirus replication, although t he precise mechanism remains to be determined.