The effect of single amino acid substitution at position 220 in the hemagglutinin glycoprotein on avian influenza H7N9 candidate vaccine virus

Liu, Liqi; Li, Zi; Zhou, Jianfang; Lü, Jian; Li, Xiyan; Liu, Jia; Xiao, Ning; Wang, Dayan

doi:10.1007/s11262-021-01827-y

Cited by 4 publications

(2 citation statements)

References 45 publications

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“…The potential exists that NAIs selective pressure can contribute to the HA antigenic evolution. Besides, the H7N9 virus (rg006/PR8) exhibited poor HI reactivity to both itself(HI:160) and its mutant(HI:40) antiserum ( Figure 6 ), which was consistent with the previous research [ 48 , 49 ]. However, after a single substitution occurred, rg006HA229I/PR8 exhibited better HI reactivity to both itself (HI:2560) and rg006/PR8(HI:640) antiserum.…”

Section: Discussionsupporting

confidence: 91%

R229I substitution from oseltamivir induction in HA1 region significantly increased the fitness of a H7N9 virus bearing NA 292K

Tang,

Zou,

Zhou

et al. 2024

Emerging Microbes & Infections

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The proportion of human isolates with reduced neuraminidase inhibitors (NAIs) susceptibility in highly pathogenic avian influenza (HPAI) H7N9 virus was high. These drug-resistant strains showed good replication capacity without serious loss of fitness. In the presence of oseltamivir, R229I substitution were found in HA1 region of the HPAI H7N9 virus before NA R292K appeared. HPAI H7N9 or H7N9/PR8 recombinant viruses were developed to study whether HA R229I could increase the fitness of the H7N9 virus bearing NA 292K. Replication efficiency was assessed in MDCK or A549 cells. Neuraminidase enzyme activity and receptor-binding ability were analyzed. Pathogenicity in C57 mice was evaluated. Antigenicity analysis was conducted through a two-way HI test, in which the antiserum was obtained from immunized ferrets. Transcriptomic analysis of MDCK infected with HPAI H7N9 24hpi was done. It turned out that HA R229I substitution from oseltamivir induction in HA1 region increased (1) replication ability in MDCK( P < 0.05) and A549( P < 0.05), (2) neuraminidase enzyme activity, (3) binding ability to both α2,3 and α2,6 receptor, (4) pathogenicity to mice(more weight loss; shorter mean survival day; viral titer in respiratory tract, P < 0.05; Pathological changes in pneumonia), (5) transcriptome response of MDCK, of the H7N9 virus bearing NA 292K. Besides, HA R229I substitution changed the antigenicity of H7N9/PR8 virus (>4-fold difference of HI titre). It indicated that through the fine-tuning of HA-NA balance, R229I increased the fitness and changed the antigenicity of H7N9 virus bearing NA 292K. Public health attention to this mechanism needs to be drawn.

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Section: Discussionsupporting

confidence: 91%

R229I substitution from oseltamivir induction in HA1 region significantly increased the fitness of a H7N9 virus bearing NA 292K

Tang,

Zou,

Zhou

et al. 2024

Emerging Microbes & Infections

Self Cite

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“…The replication of the chimeric A/B virus may not be as optimal as the wild type [12]. Despite it is known that a reduced receptor-binding a nity generally leads to the low growth of in uenza viruses [21], it remains unclear whether there are mutations of the RBS that may result in decreased or inadmissibility to chimeric CVVs replication.…”

Section: Introductionmentioning

confidence: 99%

A A212T Substitution in Hemagglutinin Impacts on the Rescue of Influenza A(H1N1)/B Chimeric Live-Attenuated Vaccine Candidate

Zhao

Sun

et al. 2023

Preprint

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The influenza virus, a viral respiratory pathogen, causes major morbidity and mortality worldwide. In this study, we compared and analyzed the effectiveness of the rescued two chimeric H1N1 vaccine strains rA/B-California/04/2009 and rA/B-California/07/2009, respectively, which expressed the hemagglutinin of A/California/07/2009 or A/California/04/2009 based on an influenza B virus master donor. The rA/B-California/07/2009 strain was rescued successfully. However, the rA/B-California/04/2009, which expressed the HA of A/California/07/2009 could hardly be generated. In substitution for alanine at residue 212 in the chimeric HA protein of rA/B-California/04/2009 virus, threonine was identified as a deleterious change. The free Gibbs energy change of mutating residue 212 reflected that threonine in site 212 caused a reduction in the stability of rA/B-California HAs. Additionally, with the analysis of binding free energy data and RMSD values of receptor analogs and two chimeric HAs, substitution 212T also conferred decreased receptor-binding avidity. These results suggested that the substitution A212T may enhance the stability and binding affinity of the chimeric H1N1 vaccine strains. This finding may help to design a live-attenuated influenza vaccine with more efficacy.

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A synthetic TLR4 agonist significantly increases humoral immune responses and the protective ability of an MDCK-cell-derived inactivated H7N9 vaccine in mice

Luo,

Zhang,

et al. 2024

Arch Virol

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The effect of single amino acid substitution at position 220 in the hemagglutinin glycoprotein on avian influenza H7N9 candidate vaccine virus

Cited by 4 publications

References 45 publications

R229I substitution from oseltamivir induction in HA1 region significantly increased the fitness of a H7N9 virus bearing NA 292K

R229I substitution from oseltamivir induction in HA1 region significantly increased the fitness of a H7N9 virus bearing NA 292K

A A212T Substitution in Hemagglutinin Impacts on the Rescue of Influenza A(H1N1)/B Chimeric Live-Attenuated Vaccine Candidate

A synthetic TLR4 agonist significantly increases humoral immune responses and the protective ability of an MDCK-cell-derived inactivated H7N9 vaccine in mice

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