Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin

IF 20.6 1区 医学 Q1 MICROBIOLOGY
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Abstract

Human influenza virus evolves to escape neutralization by polyclonal antibodies. However, we have a limited understanding of how the antigenic effects of viral mutations vary across the human population and how this heterogeneity affects virus evolution. Here, we use deep mutational scanning to map how mutations to the hemagglutinin (HA) proteins of two H3N2 strains, A/Hong Kong/45/2019 and A/Perth/16/2009, affect neutralization by serum from individuals of a variety of ages. The effects of HA mutations on serum neutralization differ across age groups in ways that can be partially rationalized in terms of exposure histories. Mutations that were fixed in influenza variants after 2020 cause greater escape from sera from younger individuals compared with adults. Overall, these results demonstrate that influenza faces distinct antigenic selection regimes from different age groups and suggest approaches to understand how this heterogeneous selection shapes viral evolution.

Abstract Image

流感血凝素突变的抗原效应随年龄变化的异质性
人类流感病毒不断进化,以逃避多克隆抗体的中和作用。然而,我们对病毒突变的抗原效应如何在人类群体中发生变化以及这种异质性如何影响病毒进化的了解十分有限。在这里,我们利用深度突变扫描绘制了两个H3N2毒株(A/香港/45/2019和A/柏斯/16/2009)的血凝素(HA)蛋白突变如何影响不同年龄个体血清中和病毒的图谱。HA突变对不同年龄组血清中和作用的影响各不相同,这在一定程度上可以用接触史来解释。与成年人相比,2020 年后固定在流感变异株中的突变在年轻人血清中的逃逸率更高。总之,这些结果表明,不同年龄组的流感面临着不同的抗原选择机制,并提出了了解这种异质性选择如何影响病毒进化的方法。
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来源期刊
Cell host & microbe
Cell host & microbe 生物-微生物学
CiteScore
45.10
自引率
1.70%
发文量
201
审稿时长
4-8 weeks
期刊介绍: Cell Host & Microbe is a scientific journal that was launched in March 2007. The journal aims to provide a platform for scientists to exchange ideas and concepts related to the study of microbes and their interaction with host organisms at a molecular, cellular, and immune level. It publishes novel findings on a wide range of microorganisms including bacteria, fungi, parasites, and viruses. The journal focuses on the interface between the microbe and its host, whether the host is a vertebrate, invertebrate, or plant, and whether the microbe is pathogenic, non-pathogenic, or commensal. The integrated study of microbes and their interactions with each other, their host, and the cellular environment they inhabit is a unifying theme of the journal. The published work in Cell Host & Microbe is expected to be of exceptional significance within its field and also of interest to researchers in other areas. In addition to primary research articles, the journal features expert analysis, commentary, and reviews on current topics of interest in the field.
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