HEMAGGLUTININ OF SWINE INFLUENZA-VIRUS - A SINGLE AMINO-ACID CHANGE PLEIOTROPICALLY AFFECTS VIRAL ANTIGENICITY AND REPLICATION
HEMAGGLUTININ OF SWINE INFLUENZA-VIRUS - A SINGLE AMINO-ACID CHANGE PLEIOTROPICALLY AFFECTS VIRAL ANTIGENICITY AND REPLICATION
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DOI：
10.1073/pnas.80.22.6996
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发表时间：
1983-01-01
期刊：
影响因子：
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通讯作者：
KILBOURNE, ED
中科院分区：
文献类型：
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作者：
BOTH, GW;SHI, CH;KILBOURNE, ED
在对携带该基因的病毒重组体（X-53a）的研究中，获得了猪流感病毒a /NJ/11/76（H1N1）株高产(H)突变体H1血凝素（HA）基因的完整核苷酸序列。这一测定结果与人流感H1N1原型病毒A/WSN/33和A/PR/8/34进行了比较，发现HA1和HA2的氨基酸同源性分别为80%和94%。已经确定了其他含有来自A/NJ/11/76的H或L（低产量表型）基因的病毒重组体的部分序列。L突变体原型的HA1区序列基本完成，与H突变体原型的HA1区序列仅相差4个氨基酸。另外4种病毒的序列分析仅限于HA的区域，推测能够区分L和H突变体的单克隆抗体与该区域发生反应。因此，这些序列的变化与病毒表型的变化有关。残基155从glly到Glu的变化与从L到H HA表型的变化有关。该位点在结构上相当于HA模型上的氨基酸158，靠近HA单体的尖端，邻近拟议的受体结合位点，因此可信地影响病毒的抗原性和复制。由于L和H两种变体都存在于自然界中，并且由于在没有免疫选择的情况下，在实验室中可以选择回复体作为复制变体，因此这些研究提供了偶然的抗原变化与生物功能变化相关的证据，这是由单个碱基变化决定的。
The complete nucleotide sequence has been obtained of the H1 hemagglutinin (HA) gene of a high-yielding (H) mutant of the A/NJ/11/76(H1N1) strain of swine influenza virus in studies of a viral reassortant (X-53a) bearing this gene. This determination has permitted comparison with human influenza H1N1 prototype viruses A/WSN/33 and A/PR/8/34, with which 80% and 94% amino acid homology was found between HA1 and HA2, respectively. Partial sequences have been determined for other viral reassortants containing either H or L (low-yielding phenotype) genes derived from A/NJ/11/76. Sequence of the HA1 region of an L mutant prototype was virtually completed and differed from that of the H mutant by only 4 amino acid changes. Sequence analysis of 4 other viruses was restricted to regions of the HA with which monoclonal antibodies capable of distinguishing L and H mutants are presumed to react. Thus, changes in these sequences are relevant to changes in viral phenotype. Change at residue 155 from Gly to Glu is associated with change from L to H HA phenotype. This site, structurally equivalent to amino acid 158 on the HA model is near the tip of the HA monomer adjacent to the proposed receptor binding site and therefore credibly could influence both viral antigenicity and replication. Because both L and H variants exist in nature and because revertants may be selected in the laboratory as replication variants in the absence of immunoselection, these studies provide evidence for fortuitous antigenic change in association with change in biological function, which is determined by a single base change.