Kiyotani K, Takao S, Sakaguchi T, Yoshida T
Department of Bacteriology, Hiroshima University School of Medicine, Japan.
Virology. 1990 Jul;177(1):65-74. doi: 10.1016/0042-6822(90)90460-9.
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 LLCMK2 cells. When a high dose of HVJpi (3.0 x 10(7) 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 LD50) immediately after inoculation. In contrast, the mice inoculated with a lower dose of HVJpi (8.2 x 10(5) 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.
研究了从携带病毒培养物中分离出的温度敏感突变株仙台病毒（HVJpi）对小鼠致死性仙台病毒（HVJ）感染的保护作用。HVJpi对强毒野生型病毒在LLCMK2细胞中的复制具有很强的干扰能力。当将高剂量的HVJpi（3.0×10⁷蚀斑形成单位）经鼻接种到小鼠体内时，小鼠既无疾病表现也无肺部病变，且在接种后立即对强毒野生型病毒（18个半数致死量）的攻击获得了显著抗性。相比之下，接种低剂量HVJpi（8.2×10⁵蚀斑形成单位）的小鼠没有表现出即时抗性，但在接种几天后产生了免疫力。肺内病毒复制的时间进程显示，高剂量HVJpi同时感染可使野生型病毒的复制强烈抑制至约千分之一，从而使所有感染小鼠的肺部病变最小化并存活。干扰素和自然杀伤细胞似乎在HVJpi介导的即时免疫状态中均未发挥主要作用，因为尽管用抗干扰素和抗去唾液酸神经节苷脂GM1抗体预处理小鼠，但与未处理的双重感染小鼠相比，同时感染野生型病毒和HVJpi的小鼠在保护方面没有差异。另一方面，通过蛋白质印迹法分析感染小鼠肺中合成的病毒多肽表明，野生型病毒在肺中复制的早期阶段主要受到HVJpi干扰能力的抑制。这些结果表明，HVJpi是一种独特的病毒突变株，能够通过接种后立即发挥干扰能力，随后诱导病毒特异性免疫反应来保护小鼠免受致死性仙台病毒感染。
