AN 18-AMINO ACID DELETION IN AN INFLUENZA NEURAMINIDASE
AN 18-AMINO ACID DELETION IN AN INFLUENZA NEURAMINIDASE
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DOI：
10.1016/0042-6822(85)90332-0
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发表时间：
1985-01-01
期刊：
影响因子：
3.7
通讯作者：
LAVER, WG
中科院分区：
文献类型：
--
作者：
ELS, MC;AIR, GM;LAVER, WG
编码流感病毒X-7（F1）的抗原变体（其含有A/RI/5+/57的NA）中的神经氨酸酶（NA）的基因比其他N2神经氨酸酶基因短。当在用单克隆抗体选择变体之前以有限稀释度克隆亲本X-7（F1）病毒时，克隆出具有较短NA基因的次要组分，并且在所有变体中保留该缺失。序列分析表明，有一个单一的缺失，54个核苷酸长，这发生在编码区的NA。缺失的18个氨基酸来自蛋白质的茎区，其是含有四聚体酶的4条多肽链的薄结构，所述四聚体酶将酶促和抗原活性头部与包埋在病毒膜中的疏水序列分开。当用电镜检查洗涤剂释放的NA的回缩时，缺失可以被看作是缩短的茎，这证实了NA茎是高度延伸的结构。尽管更丰富的血凝素（HA）可能会延伸到病毒表面上缩短的NA分子之外，但NA头部仍然可以被所有可用的单克隆抗体接近，这些单克隆抗体针对分子上的不同抗原位点。对小底物分子N-乙酰神经氨酰乳糖的酶活性对于亲本X-7（F7）病毒和具有缺失的NA的菌株是相同的;然而，后一种病毒切割大底物胎球蛋白较慢，并且以降低的速率从红细胞洗脱。
The genes coding for the neuraminidase (NA) enzyme in antigenic variants of influenza virus X-7(F1) (which contains the NA of A/RI/5+/57) are shorter than other N2 neuraminidase genes. When the parent X-7(F1) virus was cloned at limiting dilution prior to selection of variants with monoclonal antibodies, a minor component with a shorter NA gene was cloned out, and this deletion was retained in all the variants. Sequence analysis showed that there is a single deletion, 54 nucleotides long, which occurs in the coding region of the NA. The 18 deleted amino acids are from the stalk region of the protein, which is a thin structure containing the 4 polypeptide chains of the tetrameric enzyme which separates the enzymatically and antigenically active head from the hydrophobic sequence embedded in the viral membrane. The deletion can be seen as a shortened stalk when rosettes of detergent-released NA are examined by EM, which confirms that the NA stalk is a highly extended structure. Although the more abundant hemagglutinin (HA) would probably extend beyond the shortened NA molecule on the surface of the virus, the NA head is still accessible to all of the available monoclonal antibodies to the different antigenic sites on the molecule. Enzymatic activity toward a small substrate molecule, N-acetyl neuraminyl lactose, is the same for both the parental X-7(F7) virus and the strain having the deleted NA; however, the latter virus is slower to cleave a large substrate, fetuin, and elutes from red cells at a reduced rate.