CHARACTERIZATION OF TEMPERATURE SENSITIVE INFLUENZA-VIRUS MUTANTS DEFECTIVE IN NEURAMINIDASE
CHARACTERIZATION OF TEMPERATURE SENSITIVE INFLUENZA-VIRUS MUTANTS DEFECTIVE IN NEURAMINIDASE
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DOI：
10.1016/0042-6822(74)90276-1
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发表时间：
1974-01-01
期刊：
影响因子：
3.7
通讯作者：
COMPANS, RW
中科院分区：
文献类型：
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作者：
PALESE, P;TOBITA, K;COMPANS, RW
流感病毒WSN（HON1）株的两种温度敏感突变体ts3和ts11属于同一重组组，与在允许温度（33°）下生长的病毒相比，在非允许温度（39.5°）下生长时，其感染性滴度低1000至10，000倍，并且缺乏血凝和神经氨酸酶活性。在感染这些突变体的细胞中合成的病毒多肽的模式与野生型病毒相似。突变病毒的神经氨酸酶活性比野生型的酶更不稳定。尽管产量低，但在39.5°下发现形态上完整的病毒颗粒，但与在33°下生长的病毒相反，病毒的大聚集体聚集在细胞表面附近。这些聚集的病毒颗粒含有神经氨酸，如胶体铁染色所示。因此，很可能是含有神经氨酸的蛋白质作为其他病毒颗粒的血凝素的受体，导致广泛的聚集。用霍乱弧菌的神经氨酸酶处理聚集体，可恢复在39.5°生长的病毒的血凝活性。这些结果表明，在39.5°下生长的突变病毒缺乏血凝活性是表面携带神经氨酸的病毒颗粒聚集体形成的结果，并且ts缺陷存在于神经氨酸酶而不是血凝素分子中。据推测，神经氨酸酶对于流感病毒的复制是必需的，并且需要从病毒包膜去除神经氨酸以避免子代病毒的聚集。
Two temperature sensitive mutants, ts3 and ts11, of the WSN (HON1) strain of influenza virus, belonging to the same recombination group, have a 1000- to 10,000-fold lower infectivity titer and lack hemagglutinating and neuraminidase activity when grown at nonpermissive temperature (39.5°), compared with virus grown at permissive temperature (33°). The patterns of viral polypeptides synthesized in cells infected with these mutants are similar to those found with wild type virus. Neuraminidase activity of the mutant viruses is more temperature labile than the enzyme of the wild type. Despite the low yield, morphologically intact virus particles are found at 39.5°, but in contrast to virus grown at 33° large aggregates of virus accumulate near the cell surface. These aggregated virus particles contain neuraminic acid as demonstrated by a colloidal iron stain. Thus, it is likely that a neuraminic acid containing protein serves as receptor for the hemagglutinin of other virus particles, resulting in the extensive aggregation. Hemagglutinating activity of virus grown at 39.5° is restored by treatment of the aggregates with neuraminidase fromVibrio cholerae. These results suggest that the lack of hemagglutinating activity of mutant virus grown at 39.5° is a consequence of the formation of aggregates of virus particles carrying neuraminic acid on their surface, and that the ts defect is in the neuraminidase but not the hemagglutinin molecule. It is postulated that neuraminidase is essential for the replication of influenza viruses and is required to remove neuraminic acid from the viral envelope to avoid aggregation of the progeny virus.