IMMEDIATE PROTECTION OF MICE FROM LETHAL WILD-TYPE SENDAI VIRUS (HVJ) INFECTIONS BY A TEMPERATURE-SENSITIVE MUTANT, HVJPI, POSSESSING HOMOLOGOUS INTERFERING CAPACITY

IMMEDIATE PROTECTION OF MICE FROM LETHAL WILD-TYPE SENDAI VIRUS (HVJ) INFECTIONS BY A TEMPERATURE-SENSITIVE MUTANT, HVJPI, POSSESSING HOMOLOGOUS INTERFERING CAPACITY
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DOI:
10.1016/0042-6822(90)90460-9
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发表时间:
1990-07-01
期刊:
影响因子:
3.7
通讯作者:
YOSHIDA, T
YOSHIDA, T
中科院分区:
医学3区
文献类型:
--
作者:
KIYOTANI, K;TAKAO, S;YOSHIDA, T

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研究了从载体培养中分离的温度敏感突变体HVJpi对小鼠免受致命仙台病毒(HVJ)感染的保护作用。HVJpi对LLCMK2细胞中毒性野生型病毒的复制有很强的干扰能力。当高剂量的HVJpi(3.0倍。107 CIU)经鼻内分离到小鼠体内,小鼠未出现疾病和肺部病变,但在接种后立即对强毒野生型病毒(18 LD50)的攻击产生了显著的抵抗力。相比之下,小鼠接种较低剂量的HVJpi(8.2。105 CIU)未表现出立即抗性,但接种后几天产生免疫。病毒在肺内复制的时间过程表明,高剂量HVJpi同时感染时,野生型病毒的复制被强烈抑制到1/1000左右,从而使所有感染小鼠的肺部病变和生存率降到最低。干扰素和自然杀伤细胞在HVJpi的即时免疫状态中似乎都没有发挥主要作用,因为在抗干扰素和抗亚洲蓟GM1抗体预处理小鼠的地方,同时感染野生型病毒和HVJpi的小鼠与未处理的双重感染小鼠相比,在保护作用上没有差异。另一方面,通过免疫印迹法对感染小鼠肺中合成的病毒多肽进行分析,表明HVJpi的干扰能力主要抑制了野生型病毒在肺中的早期复制。这些结果表明,HVJpi是一种独特的病毒突变体,它在接种后立即具有干扰能力,然后通过诱导病毒特异性免疫反应来保护小鼠免受致命的仙台病毒感染。
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 .times. 107 CIU) was isolated 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 .times. 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 stimultaneously infected with wild-type virus and HVJpi in site 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.