Genomic signatures and host adaptation of H5N1 clade 2.3.4.4b: A call for global surveillance and multi-target antiviral strategies

The recent report of the first fatality associated with infection by influenza virus H5N1 clade 2.3.4.4b, identified as genotype D1.1, which is distinct from the B3.13 genotype, has sparked fears of a potential human pandemic. However, the genetic relationships between B3.13 and D1.1, as well as the...

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Main Authors: Guangxu Zhang, Yuren Shi, Haoyu Ge, Yuanzhou Wang, Lu Lu, Shibo Jiang, Qian Wang
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Current Research in Microbial Sciences
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666517425000392
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author Guangxu Zhang
Yuren Shi
Haoyu Ge
Yuanzhou Wang
Lu Lu
Shibo Jiang
Qian Wang
author_facet Guangxu Zhang
Yuren Shi
Haoyu Ge
Yuanzhou Wang
Lu Lu
Shibo Jiang
Qian Wang
author_sort Guangxu Zhang
collection DOAJ
description The recent report of the first fatality associated with infection by influenza virus H5N1 clade 2.3.4.4b, identified as genotype D1.1, which is distinct from the B3.13 genotype, has sparked fears of a potential human pandemic. However, the genetic relationships between B3.13 and D1.1, as well as their origins, host adaptability, and antiviral resistance, remain poorly understood. Here we conducted a comprehensive phylogenetic and comparative analysis of H5N1 clade 2.3.4.4b across multiple species, in order to identify the molecular characteristics and frequency of resistance mutations in these two genotypes, elucidate their evolutionary trajectories, and assess their implications for public health. Our results demonstrate that B3.13 exhibits mammalian adaptability, while D1.1 retains avian adaptability. Importantly, both genotypes display limited occurrences of human-like signatures, which can help alleviate public anxiety. Additionally, the emergence of the resistance mutations in the clade 2.3.4.4b on the binding sites of antivirals calls for the development of multi-target antiviral strategies to mitigate the risk of resistant strain reassortment.
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spelling doaj-art-148ee5e8289345efad44b713634fd30f2025-08-20T03:46:41ZengElsevierCurrent Research in Microbial Sciences2666-51742025-01-01810037710.1016/j.crmicr.2025.100377Genomic signatures and host adaptation of H5N1 clade 2.3.4.4b: A call for global surveillance and multi-target antiviral strategiesGuangxu Zhang0Yuren Shi1Haoyu Ge2Yuanzhou Wang3Lu Lu4Shibo Jiang5Qian Wang6Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaCorresponding authors.; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaCorresponding authors.; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaCorresponding authors.; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaThe recent report of the first fatality associated with infection by influenza virus H5N1 clade 2.3.4.4b, identified as genotype D1.1, which is distinct from the B3.13 genotype, has sparked fears of a potential human pandemic. However, the genetic relationships between B3.13 and D1.1, as well as their origins, host adaptability, and antiviral resistance, remain poorly understood. Here we conducted a comprehensive phylogenetic and comparative analysis of H5N1 clade 2.3.4.4b across multiple species, in order to identify the molecular characteristics and frequency of resistance mutations in these two genotypes, elucidate their evolutionary trajectories, and assess their implications for public health. Our results demonstrate that B3.13 exhibits mammalian adaptability, while D1.1 retains avian adaptability. Importantly, both genotypes display limited occurrences of human-like signatures, which can help alleviate public anxiety. Additionally, the emergence of the resistance mutations in the clade 2.3.4.4b on the binding sites of antivirals calls for the development of multi-target antiviral strategies to mitigate the risk of resistant strain reassortment.http://www.sciencedirect.com/science/article/pii/S2666517425000392Influenza virusH5N1 clade 2.3.4.4bGenomic signatureCross-species substitutionAntiviral resistance mutation
spellingShingle Guangxu Zhang
Yuren Shi
Haoyu Ge
Yuanzhou Wang
Lu Lu
Shibo Jiang
Qian Wang
Genomic signatures and host adaptation of H5N1 clade 2.3.4.4b: A call for global surveillance and multi-target antiviral strategies
Current Research in Microbial Sciences
Influenza virus
H5N1 clade 2.3.4.4b
Genomic signature
Cross-species substitution
Antiviral resistance mutation
title Genomic signatures and host adaptation of H5N1 clade 2.3.4.4b: A call for global surveillance and multi-target antiviral strategies
title_full Genomic signatures and host adaptation of H5N1 clade 2.3.4.4b: A call for global surveillance and multi-target antiviral strategies
title_fullStr Genomic signatures and host adaptation of H5N1 clade 2.3.4.4b: A call for global surveillance and multi-target antiviral strategies
title_full_unstemmed Genomic signatures and host adaptation of H5N1 clade 2.3.4.4b: A call for global surveillance and multi-target antiviral strategies
title_short Genomic signatures and host adaptation of H5N1 clade 2.3.4.4b: A call for global surveillance and multi-target antiviral strategies
title_sort genomic signatures and host adaptation of h5n1 clade 2 3 4 4b a call for global surveillance and multi target antiviral strategies
topic Influenza virus
H5N1 clade 2.3.4.4b
Genomic signature
Cross-species substitution
Antiviral resistance mutation
url http://www.sciencedirect.com/science/article/pii/S2666517425000392
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