Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance.

IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences
PLoS Biology Pub Date : 2024-11-12 eCollection Date: 2024-11-01 DOI:10.1371/journal.pbio.3002916
Bernadeta Dadonaite, Jenny J Ahn, Jordan T Ort, Jin Yu, Colleen Furey, Annie Dosey, William W Hannon, Amy L Vincent Baker, Richard J Webby, Neil P King, Yan Liu, Scott E Hensley, Thomas P Peacock, Louise H Moncla, Jesse D Bloom
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引用次数: 0

Abstract

H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple nonhuman mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the >10,000 different possible amino-acid mutations to HA. Here, we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine virus, and we show that a mutation present in some recent H5 HAs causes a large antigenic change. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.

对 H5 血凝素进行深度突变扫描,为流感病毒监测提供信息。
H5 流感被认为是一种潜在的大流行威胁。最近,属于 2.3.4.4b 支系的 H5 病毒在禽类和多种非人类哺乳动物中引起了大规模爆发。先前的研究已经确定了病毒血凝素(HA)蛋白的分子表型,这些表型会导致病毒在人类中的大流行,包括细胞进入、受体偏好、HA 稳定性和多克隆血清中和能力降低。然而,之前的实验工作只测量了这些表型如何受到 HA 可能发生的 10,000 多种氨基酸突变中少数几种突变的影响。在这里,我们使用伪病毒深度突变扫描来测量 2.3.4.4b H5 HA 的所有突变如何影响每种表型。我们发现了能使 HA 更好地结合 α2-6 连接的硅酸的突变,并证明一些病毒已经携带了能稳定 HA 的突变。我们还测量了所有 HA 突变如何影响接种 2.3.4.4b H5 病毒或感染 2.3.4.4b H5 病毒的小鼠和雪貂血清的中和作用。通过这些抗原图谱,我们可以快速评估新的病毒株何时获得了可能与候选疫苗病毒产生错配的突变。总之,深度突变扫描的系统性与假病毒的安全性相结合,能够全面测量突变的表型效应,为实时解读监测 H5 流感期间观察到的病毒变异提供信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
PLoS Biology
PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY
CiteScore
15.40
自引率
2.00%
发文量
359
审稿时长
3-8 weeks
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
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