The low-pH stability discovered in neuraminidase of 1918 pandemic influenza A virus enhances virus replication.
The low-pH stability discovered in neuraminidase of 1918 pandemic influenza A virus enhances virus replication.
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DOI：
10.1371/journal.pone.0015556
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发表时间：
2010-12-09
期刊：
影响因子：
3.7
通讯作者：
Suzuki T
中科院分区：
文献类型：
--
作者：
Takahashi T;Kurebayashi Y;Ikeya K;Mizuno T;Fukushima K;Kawamoto H;Kawaoka Y;Suzuki Y;Suzuki T
西班牙甲型流感大流行病毒在1918-19年期间导致全球2000多万人死亡，是有记录以来最严重的病原体之一。通过反向遗传学重建的1918年大流行病毒的特征表明，PB1、血凝素(HA)和神经氨酸酶(NA)基因对1918年大流行流感病毒的复制和毒力起作用。然而，NA基因的功能仍不清楚。在这里，我们表明，在1918年大流行病毒NA中发现的唾液酸酶活性的低pH稳定性有助于病毒复制效率。通过对1918年大流行病毒NA中435位Thr或455位Gly的缺失与1918年大流行病毒NA中唾液酸酶活性的低pH稳定性以及嵌合结构中唾液酸酶活性的比较，我们发现Thr和Gly的缺失与1918年大流行病毒NA中唾液酸酶活性的低pH稳定性有关。这两种氨基酸都位于氨基酸残基中或附近，这些氨基酸残基对低pH条件下天然四聚体结构的稳定非常重要，就像1957年和1968年出现的大流行病毒的N2Nas一样。从A/USSR/92/77(H1N1)A/WSN/33(H1N1)的遗传背景中产生了两种反向遗传病毒，包括来自A/USSR/92/77(H1N1)的低pH不稳定的N1 NA及其对应的N1 NA，其中唾液酸酶活性通过435和455位氨基酸残基的缺失和替换而转变为低pH稳定特性，这与1918NA中唾液酸酶活性的低pH稳定性有关。与含有低pH不稳定的N1 NA的变异病毒相比，含有类似“西班牙流感”的低pH稳定NA的突变病毒表现出显著的复制能力。我们的结果表明，1918年大流行病毒NA中唾液酸酶活性的低pH稳定性与病毒复制效率有关。
The “Spanish” pandemic influenza A virus, which killed more than 20 million worldwide in 1918-19, is one of the serious pathogens in recorded history. Characterization of the 1918 pandemic virus reconstructed by reverse genetics showed that PB1, hemagglutinin (HA), and neuraminidase (NA) genes contributed to the viral replication and virulence of the 1918 pandemic influenza virus. However, the function of the NA gene has remained unknown. Here we show that the avian-like low-pH stability of sialidase activity discovered in the 1918 pandemic virus NA contributes to the viral replication efficiency. We found that deletion of Thr at position 435 or deletion of Gly at position 455 in the 1918 pandemic virus NA was related to the low-pH stability of the sialidase activity in the 1918 pandemic virus NA by comparison with the sequences of other human N1 NAs and sialidase activity of chimeric constructs. Both amino acids were located in or near the amino acid resides that were important for stabilization of the native tetramer structure in a low-pH condition like the N2 NAs of pandemic viruses that emerged in 1957 and 1968. Two reverse-genetic viruses were generated from a genetic background of A/WSN/33 (H1N1) that included low-pH-unstable N1 NA from A/USSR/92/77 (H1N1) and its counterpart N1 NA in which sialidase activity was converted to a low-pH-stable property by a deletion and substitutions of two amino acid residues at position 435 and 455 related to the low-pH stability of the sialidase activity in 1918 NA. The mutant virus that included “Spanish Flu”-like low-pH-stable NA showed remarkable replication in comparison with the mutant virus that included low-pH-unstable N1 NA. Our results suggest that the avian-like low-pH stability of sialidase activity in the 1918 pandemic virus NA contributes to the viral replication efficiency.
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DOI：
10.1128/aem.16.4.588-594.1968
发表时间：
1968-01-01
期刊：
APPLIED MICROBIOLOGY
影响因子：
--
作者：
GAUSH, CR;SMITH, TF
通讯作者：
SMITH, TF
影响因子：
5.8
作者：
Ohuchi, Masanobu;Asaoka, Naoko;Ohuchi, Reiko
通讯作者：
Ohuchi, Reiko
影响因子：
64.8
作者：
Kobasa, D;Takada, A;Kawaoka, Y
通讯作者：
Kawaoka, Y
影响因子：
5.3
作者：
DUBRIDGE, RB;TANG, P;CALOS, MP
通讯作者：
CALOS, MP
DOI：
10.1016/0167-4838(91)90526-6
发表时间：
1991-03-08
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
CHONG, AKJ;PEGG, MS;VONITZSTEIN, M
通讯作者：
VONITZSTEIN, M