Dynamics of glycoprotein charge in the evolutionary history of human influenza.
Dynamics of glycoprotein charge in the evolutionary history of human influenza.
复制标题
糖蛋白电荷的动力学在人类流感的进化史上。
DOI：
10.1371/journal.pone.0015674
复制
发表时间：
2010-12-30
期刊：
影响因子：
3.7
通讯作者：
Grenfell B
中科院分区：
文献类型：
--
作者：
Arinaminpathy N;Grenfell B
流感病毒表现出显著的逃避宿主免疫的能力;这表现为病毒表面分子的抗原表型的大的偶然跳跃和导致人类每年流感流行的逐渐抗原变化。最近的小鼠研究表明，对宿主细胞的亲合力可以在多克隆抗体逃逸中发挥重要作用，并且进一步地，血凝素糖蛋白的静电电荷可以有助于这种亲合力。我们使用一种简单的计算净糖蛋白电荷的方法，测试了糖蛋白电荷对人类甲型流感病毒三种主要亚型序列数据的作用。在所有亚型中，H3N2在人类中显示出自1968年引入以来正电荷增加的惊人模式。值得注意的是，这种趋势适用于血凝素和神经氨酸酶糖蛋白。在20世纪80年代后期，血凝素电荷达到一个平台，而神经氨酸酶电荷开始下降。我们确定了参与这种电荷趋势的氨基酸位点的关键组。据我们所知，这些是第一个迹象表明，人类H3N2，净糖蛋白电荷协变强烈的抗原漂移在全球范围内。需要进一步的工作来阐明这种电荷如何与其他免疫逃逸机制，如糖基化相互作用，我们讨论了未来研究中出现的重要问题。
Influenza viruses show a significant capacity to evade host immunity; this is manifest both as large occasional jumps in the antigenic phenotype of viral surface molecules and in gradual antigenic changes leading to annual influenza epidemics in humans. Recent mouse studies show that avidity for host cells can play an important role in polyclonal antibody escape, and further that electrostatic charge of the hemagglutinin glycoprotein can contribute to such avidity. We test the role of glycoprotein charge on sequence data from the three major subtypes of influenza A in humans, using a simple method of calculating net glycoprotein charge. Of all subtypes, H3N2 in humans shows a striking pattern of increasing positive charge since its introduction in 1968. Notably, this trend applies to both hemagglutinin and neuraminidase glycoproteins. In the late 1980s hemagglutinin charge reached a plateau, while neuraminidase charge started to decline. We identify key groups of amino acid sites involved in this charge trend. To our knowledge these are the first indications that, for human H3N2, net glycoprotein charge covaries strongly with antigenic drift on a global scale. Further work is needed to elucidate how such charge interacts with other immune escape mechanisms, such as glycosylation, and we discuss important questions arising for future study.