ANTIGENIC VARIATION IN 3 DISTINCT DETERMINANTS OF AN INFLUENZA TYPE-A HEMAGGLUTININ MOLECULE
ANTIGENIC VARIATION IN 3 DISTINCT DETERMINANTS OF AN INFLUENZA TYPE-A HEMAGGLUTININ MOLECULE
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DOI：
10.1038/279246a0
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发表时间：
1979-01-01
期刊：
影响因子：
64.8
通讯作者：
GERHARD, WU
中科院分区：
文献类型：
--
作者：
YEWDELL, JW;WEBSTER, RG;GERHARD, WU
尽管针对许多人类病毒病原体的疫苗已经开发出来，但针对甲型流感病毒的疫苗接种还没有完全成功。这主要是由于病毒表面蛋白，血凝素和神经氨酸酶，受到抗原进化的影响。抗原性的主要变化（抗原性转移）可归因于：(1)抗原性不同的流感病毒之间偶尔发生基因重组，或(2)以前流行的流感病毒重新传入人群。相反，次要的抗原变异（抗原漂移）被认为是由病毒复制过程中自发的点突变引起的，随后在部分免疫的宿主群体中选择突变体。血凝素分子中的抗原漂移在流行病学上比神经氨酸酶分子中的抗原漂移更重要，这可能是因为免疫机制通过与血凝素分子的相互作用来中和病毒。因此，抗原漂移的先决条件似乎是血凝素分子抗原结构的高突变率。在本研究中，用单克隆抗体测定克隆病毒制剂中存在的抗原突变病毒的频率。结果发现，A/PR/8/34 （h1n1）血凝素分子单个决定因子的抗原变化平均发生频率为每感染一次病毒10−6次，并且本文描述的三个决定因子相互独立地发生突变。讨论了这些观察结果的流行病学意义。
ALTHOUGH vaccines have been developed against many human viral pathogens, vaccination against influenza type A viruses has not been wholly successful. This is mainly due to the fact that the viral surface proteins, haemagglutinin and neuraminidase, are subject to antigenic evolution1. Major changes in antigenicity (antigenic shifts) are attributed to (1) the occasional occurrence of genetic reassortment between antigenically dissimilar influenza viruses, or (2) the re-introduction of a previously prevalent influenza virus into the human population. In contrast, minor antigenic variation (antigenic drift) is thought to result from spontaneous point mutations during virus replication followed by the selection of mutants in a partially immune host population. Antigenic drift in the haemagglutinin molecule is epidemiologically of greater importance than that in the neuraminidase molecule, probably because immune mechanisms neutralise virus through interaction with the haemagglutinin molecule. It seems, therefore, that a prerequisite of antigenic drift is a high mutation rate in the antigenic structures of the haemagglutinin molecule. In the present study, the frequency of antigenic mutant viruses present in cloned virus preparations was determined by means of monoclonal antibodies. It was found that antigenic changes in individual determinants of the haemagglutinin molecule of A/PR/8/34 (H0N1) occurred with an average frequency of 10−6per infectious dose of virus and that the three determinants described here mutated independently of each other. The epidemiological significance of these observations is discussed.