|
Basic Characteristics of Mutations
|
|
Mutation Site
|
A160T |
|
Mutation Site Sentence
|
This tree enables immediate identification of subclades with antigenic mutations with reduced neutralization, including clades defined by mutations P128S, A160T/S, and P162Q, which are present in some clusters of sequences from the ongoing dairy cattle outbreak in the United States. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
HA |
|
Standardized Encoding Gene
|
HA
|
|
Genotype/Subtype
|
H5N1 |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Influenza A
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
America |
|
Literature Information
|
|
PMID
|
39531474
|
|
Title
|
Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance
|
|
Author
|
Dadonaite B,Ahn JJ,Ort JT,Yu J,Furey C,Dosey A,Hannon WW,Vincent Baker AL,Webby RJ,King NP,Liu Y,Hensley SE,Peacock TP,Moncla LH,Bloom JD
|
|
Journal
|
PLoS biology
|
|
Journal Info
|
2024 Nov 12;22(11):e3002916
|
|
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 alpha2-6-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.
|
|
Sequence Data
|
-
|
|
|