Antibody recognition of the influenza virus neuraminidase.
Antibody recognition of the influenza virus neuraminidase.
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流感病毒神经氨酸酶的抗体识别。
DOI：
10.1101/sqb.1989.054.01.031
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Luo,M
中科院分区：
文献类型：
--
作者：
Air,GM;Laver,WG;Webster,RG;Els,MC;Luo,M
流感病毒神经氨酸酶(NA)是第一个被发现是病毒的组成部分并由病毒基因组编码的酶。它仍然是分子水平上最具特性的病毒酶之一，尽管它在病毒感染中的作用仍不清楚。NA从细胞表面的糖偶联物中裂解末端N-乙酰神经氨酸(唾液酸)。由于唾液酸是流感病毒血凝素(HA)最初与宿主细胞结合的受体，NA是一种破坏受体的酶。它允许病毒从受感染细胞的表面释放，并通过从HA上的复杂碳水化合物中裂解唾液酸来防止自我聚集(Palese等人。1974年；Basak等人。1985年)。NA还可能通过从覆盖在呼吸道上皮细胞上的粘蛋白中分解唾液酸来帮助病毒传播和接触新细胞。尽管NA的这些功能的相对重要性还没有被很好地理解，NA诱导的抗体可以预防致命的流感病毒(Webster等人。(1988年)。NA是嵌入病毒粒子脂膜的两个表面糖蛋白尖峰之一(另一个是受体结合部分，HA)。NA约占病毒蛋白的5%-10%，在电子显微镜下可见蘑菇状突起。它是一个四聚体，有一个盒状的头部，100·100×60/~，由四个共面的，大致相同的球状亚基组成，中心连接的茎通过靠近多肽氨基末端的疏水区域固定在病毒膜上(图1)。这与流感HA不同，HA是由靠近羧基末端的疏水序列锚定的。没有发生NA多肽的翻译后切割，没有信号肽被分离，甚至启动蛋氨酸也被保留(Blok等人。1982年)。在羧基末端也没有加工；从N2NA的基因序列预测的羧基末端序列Met-Pro-Ile在从病毒分离的完整NA分子中被发现。NA多肽氨基末端的六个极性氨基酸序列，在九种不同的甲型流感NA亚型中完全保守(Blok和Air 1982；Air等人)。1985年a)，但不是在B型流感中(Shaw等人。1982)，之后是一系列疏水氨基酸，必须代表NA的跨膜区(Fields等人。(1981年)。这个序列在亚型之间完全不保守(除了疏水性的保守)。对于生化研究，NA的一种可溶形式可以通过用蛋白酶处理从病毒颗粒中释放出来，这会在所示位置裂解多肽(图1)，移除茎并释放在某些情况下可以结晶的NA的酶活性和抗原性头部(Laver 1978)。病毒是通过“短”的NA分子获得的，在这种分子中，茎被删除了多达18个氨基酸，几乎是长度的50%(Els等人。1985年)。用X射线结晶学测定了两个流感病毒NAS的三维结构，并以3/~分辨率发表(Varghese等人。1983年；贝克等人。1987)。此后进行了进一步的改进(Tulip等人，本卷)。甲型和乙型流感病毒基因组由8个片段组成的负义单链RNA，以某种未知的机制有序地包装在病毒粒子内。每个片段编码一种主要的病毒蛋白，在某些情况下，次要蛋白也被编码，使用重叠的阅读框架(参见Lamb和Choppin 1983)。NA由第六大RNA片段编码。每一种病毒基因都已被…
Influenza virus neuraminidase (NA) was the first enzyme found to be an integral part of a virus and coded by the viral genome. It remains one of the bestcharacterized viral enzymes at the molecular level, although its role in viral infection is still not well understood. NA cleaves terminal N-acetyl neuraminic acid (sialic acid) from glycoconjugates on the cell surface. Because sialic acid is the receptor to which influenza virus hemagglutinin (HA) initially binds on the host cell, NA is a receptor-destroying enzyme. It allows virus to be released from the surface of infected cells and prevents self-aggregation by cleaving sialic acid from the complex carbohydrates on the HA (Palese et al. 1974; Basak et al. 1985). NA may also assist in virus spread and access to new cells by cleaving sialic acid from the mucins that overlie the epithelial cells of the respiratory tract. Although the relative importance of these functions of NA are not well understood, NA induces antibodies that protect against lethal influenza viruses (Webster et al. 1988). NA is one of two surface glycoprotein spikes (the other being the receptor-binding moiety, HA) embedded in the lipid envelope of the virion. NA accounts for about 5-10% of the virus protein and is seen in the electron microscope as a mushroom-shaped protrusion. It is a tetramer with a box-shaped head, 100• 100 x 60/~,, made of four coplanar, roughly spherical identical subunits with a centrally attached stalk anchored in the virus membrane by a hydrophobic region near the amino-terminal end of the polypeptide (Fig. 1). This contrasts with the influenza HA, which is anchored by a hydrophobic sequence near the carboxyl terminus. No posttranslational cleavage of the NA polypeptide occurs, no signal peptide is split off, and even the initiating methionine is retained (Blok et al. 1982). Nor is there processing at the carboxyl terminus; the carboxyterminal sequence Met-Pro-Ile, predicted from the gene sequence for N2 NA, is found in intact NA molecules isolated from the virus. A sequence of six polar amino acids at the amino terminus of the NA polypeptide, which are totally conserved in each of the nine different influenza A NA subtypes (Blok and Air 1982; Air et al. 1985a) but not in influenza B (Shaw et al. 1982), is followed by a sequence of hydrophobic amino acids that must represent the transmembrane regions of the NA (Fields et al. 1981). This sequence is not conserved at all between subtypes (apart from conservation of hydrophobicity). For biochemical studies, a soluble form of the NA can be released from the virus particles by treatment with proteinases, which cleave the polypeptide in the positions shown (Fig. 1), removing the stalk and releasing the enzymatically and antigenically active head of the NA, which can be crystallized in some cases (Laver 1978). Viruses have been obtained with" stubby" NA molecules in which the stalk is shortened by deletions of up to 18 amino acids, which is nearly 50% of the length (Els et al. 1985). The three-dimensional structures of two influenza NAs have been determined by X-ray crystallography and published at 3/~ resolution (Varghese et al. 1983; Baker et al. 1987). Further refinement has since been done (Tulip et al., this volume). The genome of the influenza A and B viruses consists of single-stranded RNA of negative sense existing in eight pieces, packaged in orderly fashion within the virion by some as yet unknown mechanism. Each piece codes for one of the major viral proteins, and in some cases, minor proteins are also coded, using overlapping reading frames (for review, see Lamb and Choppin 1983). NA is coded by the sixth largest RNA segment. Each of the viral genes has been …