Interferon induction by lymphocytic choriomeningitis viruses correlates with maximum virulence

Lymphocytic choriomeningitis (LCM) viruses isolated from the blood of persistently infected mice, could be clearly divided into two categories by observing the disease patterns they produced after intracerebral (i.c.) injection in a number of adult inbred and outbred mice. One type (aggressive) caused the classic pattern of convulsive death in 100% of the mice 7 to 9 days after infection, while the other (docile) caused a protracted disease with deaths occurring, if at all, 2 to 4 weeks after infection. Interferon could be detected in the serum of adult mice on the 3rd and 4th day after infection with several independently cloned aggressive, but not docile, viruses. The inability of docile virus to induce interferon was not due to poor or delayed virus replication in the brain. The aggressive pattern of disease could be provoked easily in docile virus-infected mice with the interferon inducers poly(rI) . poly(rC), tilorone hydrochloride or Newcastle disease virus. The amount of interferon produced had little effect on the mean day of death. Mice that differed over 10-fold in their serum interferon levels after LCM infection, either by genetic predisposition or by stimulation with increasing amounts of poly(rI) . poly(rC), presented almost identical patterns of mortality.