Mouse adaptation of H6 avian influenza viruses and their molecular characteristics

Wan, Zhimin; Gong, Jianxi; Sang, Jianjun; Jiang, Wenjie; Zhao, Zhehong; Lian, Mingjun; Tang, Ting; Li, Yafeng; Kan, Qiuqi; Xie, Quan; Li, Tuofan; Shao, Hongxia; Gao, Wei; Qin, Aijian; Ye, Jianqiang

doi:10.3389/fmicb.2022.1049979

Cited by 3 publications

(7 citation statements)

References 38 publications

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“…Previous studies have shown that MA E-Teal/417 mainly binds to α-2.3 sialic acid (SA) ( 18 ). To determine whether amino acid substitutions of the escape mutants alter the viral receptor-binding preference, the escape mutants, m1A5 (targeting residue 69), m2C5 (targeting residue 149), m3B9 (targeting residue 139), m4C2 (targeting residue 140), m4B8 (targeting residues 120, 124, and 246), m611 (targeting residues 69 and 221), m6E3 (targeting residue 89), were tested with two receptor analogs, i.e., Neu5Acα2–3Galb1-4GlcNAcb (3′SLN) and Neu5Acα2–6Galb 1–4GlcNAcb (6′SLN), for receptor-binding preference.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The virus MA E-Teal/417 used for selection of escape mutants was generated through adaptation of E-Teal/417 in BALB/c mice ( 18 ). Compared with wild-type E-Teal/417, MA E-Teal/417 has the G124R mutation in HA ( 18 ). Interestingly, the position 124 is targeted by MAb 4B8, residue 124 of m4B8 returns to G in HA, indicating that the residue 124 of E-Teal/417 is not only a key residue of antigenic epitope but also a virulence marker.…”

Section: Discussionmentioning

confidence: 99%

“…In 2013, a case of human infection with H6N1 virus was reported in Taiwan ( 16 ). In addition, several mutations in H6 viruses have been identified as virulence factors in mice ( 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

“…In the present study, we generated and characterized a panel of murine monoclonal antibodies (MAbs) against the HA of a mouse-adapted H6N2 strain, which was isolated from wild bird and adapted in BALB/c mice ( 18 , 25 ). Moreover, we mapped HA key residues of antigenic epitopes by selecting escape mutants for these MAbs and tested the protection of MAbs 4C2 and 6E3 against mouse-adapted A/Eurasian teal/Jiangxi/2018WB0417(H6N2) (MA E-Teal/417) challenge in a mouse model.…”

Section: Introductionmentioning

confidence: 99%

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Identification of key residues of B cell epitopes in hemagglutinin of H6 influenza A virus

Wan,

Gong,

Sang

et al. 2023

Microbiol Spectr

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H6 influenza A viruses are enzootic and genetically diverse in both domestic poultry and wild birds, occasionally causing spillovers to mammals, including humans, posing threat to public health. However, the antigenic sites of the hemagglutinin (HA) of H6 are poorly understood. In this study, a panel of murine monoclonal antibodies (MAbs) with different reactivity spectra against HA of H6 was generated and nine key residues of antigenic epitopes in H6 were identified through escape mutants of these MAbs. Of these, residues 139 and 140 belonged to antigenic Sa, residue 89 belonged to antigenic Cb, residue 149 belonged to Ca2, while residue 221 belonged to Ca1 regarding the H1 antigenic sites. However, the other four residues 69, 120, 124, and 246 were not located in the identified antigenic regions of H1. Although most HA variants of the escape mutants had the preference for avian-like receptor, whereas escape mutants m3B9 and m4C2 increased the binding affinity for both avian and human-like receptors, and m1A5 and m6D11 decreased the binding affinity for avian-like receptors. Moreover, a single dose of MAbs 4C2 or 6E3 could fully protect mice against lethal challenge of mouse-adapted A/Eurasian teal/Jiangxi/2018WB0417(H6N2) (MA E-Teal/417) in the prophylactic treatment and also could provide partial protection in the therapeutic treatment. Overall, the generated MAbs and the identified key residues of antigenic epitopes not only provide novel insights into the key markers for monitoring the antigenic variation of H6 but also demonstrate the potential for developing MAb-based passitive treatments for H6. IMPORTANCE Since the escape immunity of influenza A viruses (IAVs) is mainly caused by the continuous antigenic variations in HA, the identification of key antigenic epitopes is crucial for better understanding of the escape immunity and vaccine development for IAVs. The antigenic sites of several HA subtypes, including H1, H3, H5, and H9, have been well characterized, whereas those of H6 subtype are poorly understood. Here, we mapped nine key residues of antigenic epitopes in H6 through escape mutants using a panel of MAbs. Moreover, MAbs 4C2 and 6E3, targeting 140 and 89 residues, respectively, could protect mice against lethal challenge of MA E-Teal/417. These key residues of antigenic epitopes identified here provide the molecular targets for further elucidating the antigenic evolution of H6 and better preparing the vaccine against H6 IAV.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of key residues of B cell epitopes in hemagglutinin of H6 influenza A virus

Wan,

Gong,

Sang

et al. 2023

Microbiol Spectr

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Global distribution, receptor binding, and cross-species transmission of H6 influenza viruses: risks and implications for humans

Yan,

Li,

Huang

et al. 2023

J Virol

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The H6 subtype of avian influenza virus (AIV) is a pervasive subtype that is ubiquitously found in both wild bird and poultry populations across the globe. Recent investigations have unveiled its capacity to infect mammals, thereby expanding its host range beyond that of other subtypes and potentially facilitating its global transmission. This heightened breadth also endows H6 AIVs with the potential to serve as a genetic reservoir for the emergence of highly pathogenic avian influenza strains through genetic reassortment and adaptive mutations. Furthermore, alterations in key amino acid loci within the H6 AIV genome foster the evolution of viral infection mechanisms, which may enable the virus to surmount interspecies barriers and infect mammals, including humans, thus posing a potential threat to human well-being. In this review, we summarize the origins, dissemination patterns, geographical distribution, cross-species transmission dynamics, and genetic attributes of H6 influenza viruses. This study holds implications for the timely detection and surveillance of H6 AIVs.

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Characterization and Pathogenicity of Novel Reassortment H6N6 Avian Influenza Viruses in Southern China

Zhu,

He,

Chen

et al. 2024

Transboundary and Emerging Diseases

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The H6N6 avian influenza virus (AIV) subtype is one of the most frequently isolated subtypes in poultry, and it has a broad host range. Some strains can overcome species barriers for transmission and infect humans. Increased affinity for human‐type receptors is a key factor in this process. In this study, two H6N6 AIV strains originating from five different clades, in which amino acid 226 of hemagglutinin was mutated from glutamine to lysine, were isolated from ducks. The receptor‐binding preference and pathogenicity of the two strains in poultry and mice were evaluated. The results indicated that the DK/GD/W3 strain can bind to both α‐2,6 and α‐2,3 receptors, whereas the DK/GD/L31 strain maintained affinity toward avian‐origin α‐2,3 receptors, highlighting differences in receptor tropism and pathogenicity to different hosts for two H6N6 strains with the same genetic background. These findings have revealed the complex recombination characteristics and molecular characteristics of H6N6 circulating strains in the environment and underscored the importance of continuous surveillance of this subtype for livestock and poultry health as well as human safety.

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Mouse adaptation of H6 avian influenza viruses and their molecular characteristics

Cited by 3 publications

References 38 publications

Identification of key residues of B cell epitopes in hemagglutinin of H6 influenza A virus

Identification of key residues of B cell epitopes in hemagglutinin of H6 influenza A virus

Global distribution, receptor binding, and cross-species transmission of H6 influenza viruses: risks and implications for humans

Characterization and Pathogenicity of Novel Reassortment H6N6 Avian Influenza Viruses in Southern China

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