Immediate protection of mice from lethal wild-type Sendai virus (HVJ) infections by a temperature-sensitive mutant, HVJpi, possessing homologous interfering capacity

Abstract

Protection of mice from lethal Sendai virus (HVJ) infections by a temperature-sensitive mutant, HVJpi, which was isolated from a carrier culture, was studied. HVJpi had a strong interfering capacity with the replication of virulent wild-type virus in LLCMK 2 cells. When a high dose of HVJpi (3.0 x 107 CIU) was inoculated intranasally into mice, the mice showed neither illness nor lung lesions but gained significant resistance against the challenge of virulent wild-type virus (18 LD 50) immediately after inoculation. In contrast, the mice inoculated with a lower dose of HVJpi (8.2 x 105 CIU) did not show the immediate resistance but became immune several days after inoculation. Time courses of the virus replication in the lung revealed that the replication of wild-type virus was strongly suppressed to about 1 /1000 by the simultaneous infection with a high dose of HVJpi, thus resulting in minimizing the lung lesions and survival of all the mice infected. Neither interferon nor natural killer cells appeared to play a major role in the immediate immune status by HVJpi, since no difference was observed in protection of mice simultaneously infected with wild-type virus and HVJpi in spite of pretreatment of the mice with anti-interferon and anti-asialo GM1 antibodies as compared with that of the untreated doubly infected mice. On the other hand, it was suggested by analysis of viral polypeptides synthesized in the lung of infected mice by Western blotting that the early stage of replication of wild-type virus in the lung was inhibited mainly by the interfering capacity of HVJpi. These results indicate that HVJpi is an unique virus mutant which is capable of protecting mice from lethal Sendai virus infections by its interfering capacity immediately after inoculation and then by the induction of virus-specific immune responses.