The cytoplasmic tail of influenza A virus neuraminidase (NA) affects NA incorporation into virions, virion morphology, and virulence in mice but is not essential for virus replication
The cytoplasmic tail of influenza A virus neuraminidase (NA) affects NA incorporation into virions, virion morphology, and virulence in mice but is not essential for virus replication
复制标题
DOI：
10.1128/jvi.70.2.873-879.1996
复制
发表时间：
1996-02-01
影响因子：
5.4
通讯作者：
Kawaoka, Y
中科院分区：
文献类型：
--
作者：
Mitnaul, LJ;Castrucci, MR;Kawaoka, Y
在这项研究中，我们研究了保守的神经氨酸酶（NA）胞质尾残基在流感病毒复制中的作用，（A/WSN/33 [H1N1]）的NA胞质尾区缺失。所得病毒命名为NOTAIL，仅含有保守的6个氨基末端残基的起始甲硫氨酸，突变体病毒比野生型病毒更不容易生长，产生更小的噬斑。尽管NOTAIL突变体和野生型病毒的NA细胞表面表达水平相似，但突变体NA分子掺入病毒粒子的水平降低了86%。这种减少导致每个病毒粒子的NA活性降低，导致在感染细胞表面形成子代突变病毒粒子的大聚集体。在跨膜结构域中含有额外突变（Ser-12至Pro）的NOTAIL病毒将比NOTAIL亲本多三倍的NA分子掺入病毒粒子中，但约为野生型病毒掺入量的一半。结果表明，NA的胞质尾区不是病毒复制所必需的，但它对NA的掺入有重要影响，从而影响子代病毒的聚集性和毒力。另外，NOTAIL突变体形成的长丝状颗粒相对丰富，与大部分球形野生型颗粒相比，表明NA胞质尾区在病毒粒子形态发生中的作用。
In this study, we investigated the role of the conserved neuraminidase (NA) cytoplasmic tail residues in influenza virus replication, Mutants of influenza A virus (A/WSN/33 [H1N1]) with deletions of the NA cytoplasmic tail region were generated by reverse genetics, The resulting viruses, designated NOTAIL, contain only the initiating methionine of the conserved six amino-terminal residues, The mutant viruses grew much less readily and produced smaller plaques than did the wild-type virus, Despite similar levels of NA cell surface expression by the NOTAIL mutants and wild-type virus, incorporation of mutant NA molecules into virions was decreased by 86%. This reduction resulted in less NA activity per virion, leading to the formation of large aggregates of progeny mutant virions on the surface of infected cells, A NOTAIL virus containing an additional mutation (Ser-12 to Pro) in the transmembrane domain incorporated three times more NA molecules into virions than did the NOTAIL parent but approximately half of the amount incorporated by the wild-type virus. However, aggregation of the progeny virions still occurred at the cell surface, All NOTAIL viruses were attenuated in mice, We conclude that the cytoplasmic tail of NA is not absolutely essential for virus replication hut exerts important effects on the incorporation of NA into virions and thus on the aggregation and virulence of progeny virus, In addition, the relative abundance of long filamentous particles formed by the NOTAIL mutants, compared with the largely spherical wild-type particles, indicates a role for the NA cytoplasmic tail in virion morphogenesis.