首页> 外文期刊>Infection and immunity >Evaluation of a phenotypic revertant of the A/Alaska/77-ts-1A2 reassortant virus in hamsters and in seronegative adult volunteers: further evidence that the temperature-sensitive phenotype is responsible for attenuation of ts-1A2 reassortant viruses.
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Evaluation of a phenotypic revertant of the A/Alaska/77-ts-1A2 reassortant virus in hamsters and in seronegative adult volunteers: further evidence that the temperature-sensitive phenotype is responsible for attenuation of ts-1A2 reassortant viruses.

机译:评估仓鼠中A / Alaska / 77-TS-1A2反弹病毒的表型还原剂和血清基因成人志愿者:进一步证据表明温度敏感表型负责衰减TS-1A2重配病毒。

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In a previous study, a seronegative child to whom attenuated A/Alaska/77-ts-1A2 virus was administered (37 degrees C shutoff temperature for plaque formation) shed virus with an altered temperature-sensitive (ts) phenotype (40 degrees C shutoff temperature) (Murphy et al., Ann. N.Y. Acad. Sci. 354:172-182, 1980; Tolpin et al., Virology 112:505-517, 1981). This ts+ virus (FV1319) was evaluated for its level of replication in hamsters and for its virulence for humans. In hamsters, FV1319 ts+ virus replicated to the same level in the nasal turbinates as that of which the A/Alaska/77 wild-type virus replicated, but its replication in the lungs was reduced 40-fold. In contrast, the A/Alaska/77-ts-1A2 reassortant achieved a titer in hamster nasal turbinates that was significantly lower (P less than 0.005) than those achieved by the wild-type and the FV1319 viruses; the A/Alaska/77-ts-1A2 reassortant was not recoverable from the lungs. In seronegative adult volunteers, the pattern of replication of the FV1319 virus was similar to that of the A/Alaska/77 wild-type virus. The illness induced by the FV1319 ts+ virus was also similar to that caused by the wild-type virus. In contrast, the A/Alaska/77-ts-1A2 reassortant was satisfactorily attenuated in adult volunteers. These results suggest that attenuation of the A/Alaska/77-ts-1A2 reassortant virus in humans is a function of the ts phenotype: loss of this phenotype restored virulence. The ability of the A/Alaska/77-ts-1A2 reassortant to lose its ts phenotype and regain virulence during growth in a permissive host limits the usefulness of the ts-1A2 reassortants as vaccine viruses for humans.
机译:在先前的研究中,施用衰减A / Alaska / 77-TS-1A2病毒的血清腺儿童(用于斑块形成的37摄氏度温度),具有改变的温度敏感(TS)表型(40摄氏度温度)(Murphy等人,Ann。纽约州立道语。SCI。354:172-182,1980; Tolpin等,病毒学112:505-517,1981)。评估TS +病毒(FV1319)在仓鼠中的复制水平和对人类的毒力评估。在仓鼠中,FV1319 TS +病毒复制到鼻腔内的相同水平,因为其复制的A / Alaska / 77野生型病毒,但其在肺中的复制减少了40倍。相反,A / Alaska / 77-TS-1A2重新级定位在仓鼠鼻腔内的滴度,显着降低(p小于0.005),而不是通过野生型和FV1319病毒实现的滴度; A / Alaska / 77-TS-1A2重配位不从肺部恢复。在血清等成人志愿者中,FV1319病毒的复制模式类似于A / Alaska / 77野生型病毒的复制模式。 FV1319TS +病毒诱导的疾病也与野生型病毒引起的疾病。相反,A / Alaska / 77-TS-1A2在成人志愿者中令人满意地衰减重排。这些结果表明,人类中A / Alaska / 77-TS-1A2重配病毒的衰减是TS表型的函数:这​​种表型的丧失恢复了毒力。 A / Alaska / 77-TS-1A2重新排序的能力失去其TS表型并恢复允许在允许宿主中生长期间的毒力限制了TS-1A2重新分配作为人类疫苗病毒的有用性。

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