The emergence of new antigen branches of H9N2 avian influenza virus in China due to antigenic drift on hemagglutinin through antibody escape at immunodominant sites

Zhang, Nan; Quan, Keji; Chen, Zixuan; Hu, Qun; Nie, Ming; Xu, Nuo; Gao, Ruyi; Wang, Xiaoquan; Qin, Tao; Chen, Sujuan; Peng, Daxin; Liu, Xiufan

doi:10.1080/22221751.2023.2246582

Cited by 19 publications

(4 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since 2007, h9.4.2.5-branched AIVs have dominated the H9N2 AIV population ( Figure 1 and Table 1 ). Despite numerous efforts, this branch of viruses still continued to be prevalent in immunized flocks [ 21 , 27 , 40 ]. What enables them to have such powerful fitness is a question worth exploring.…”

Section: Discussionmentioning

confidence: 99%

Hemagglutinin glycosylation pattern-specific effects: implications for the fitness of H9.4.2.5-branched H9N2 avian influenza viruses

Sun,

Zhu,

Zhang

et al. 2024

Emerging Microbes & Infections

View full text Add to dashboard Cite

Since 2007, h9.4.2.5 has emerged as the most predominant branch of H9N2 avian influenza viruses (AIVs) that affects the majority of the global poultry population. The spread of this viral branch in vaccinated chicken flocks has not been considerably curbed despite numerous efforts. The evolutionary fitness of h9.4.2.5-branched AIVs must consequently be taken into consideration. The glycosylation modifications of hemagglutinin (HA) play a pivotal role in regulating the balance between receptor affinity and immune evasion for influenza viruses. Sequence alignment showed that five major HA glycosylation patterns have evolved over time in h9.4.2.5-branched AIVs. Here, we compared the adaptive phenotypes of five virus mutants with different HA glycosylation patterns. According to the results, the mutant with 6 N-linked glycans displayed the best acid and thermal stability and a better capacity for multiplication, although having a relatively lower receptor affinity than 7 glycans. The antigenic profile between the five mutants revealed a distinct antigenic distance, indicating that variations in glycosylation level have an impact on antigenic drift. These findings suggest that changes in the number of glycans on HA can not only modulate the receptor affinity and antigenicity of H9N2 AIVs, but also affect their stability and multiplication. These adaptive phenotypes may underlie the biological basis for the dominant strain switchover of h9.4.2.5-branched AIVs. Overall, our study provides a systematic insight into how changes in HA glycosylation patterns regulate the evolutionary fitness and epidemiological dominance drift of h9.4.2.5-branched H9N2 AIVs, which will be of great benefit for the glycosylation-dependent vaccine design.

show abstract

Section: Discussionmentioning

confidence: 99%

Hemagglutinin glycosylation pattern-specific effects: implications for the fitness of H9.4.2.5-branched H9N2 avian influenza viruses

Sun,

Zhu,

Zhang

et al. 2024

Emerging Microbes & Infections

View full text Add to dashboard Cite

show abstract

“…While vaccination remains the primary preventive strategy, antigenic variation of the virus and vaccine immune escape pose increasing challenges (Zhang et al, 2023b, de Vries et al, 2018.…”

Section: Introductionmentioning

confidence: 99%

Oxymatrine Modulation of TLR3 Signaling Pathway: A Dual-Action Mechanism against H9N2 Avian Influenza Virus and Immune Regulation

Zhi,

Liu,

Shen

et al. 2024

Preprint

View full text Add to dashboard Cite

Background H9N2 Avian Influenza Virus (AIV) poses a growing public health threat due to its rapid mutation rate and limited vaccine efficacy. Pulmonary Microvascular Endothelial Cells (PMVECs) play a critical role as a gateway for infection, highlighting the need for alternative therapeutic strategies. This study examines the antiviral potential of Oxymatrine (OMT), a traditional Chinese medicine derivative, against H9N2 AIV in PMVECs. Purpose The aim of this study is to explore the efficacy of OMT in modulating antiviral responses and to elucidate its impact on the TLR3 signaling pathway in PMVECs infected with H9N2 AIV. Study Design and Methods: Using an array of in vitro assays such as TCID50, CCK-8, RT-qPCR, ELISA, and Western blot, this study evaluated the viral infectivity, cell viability, gene and protein expression levels, and key cytokine levels in PMVECs. Additionally, RNAi technology was employed to silence TLR3 genes to further understand the mechanisms involved. Results OMT displayed a dose-dependent inhibitory effect on vital antiviral proteins PKR and Mx1 and modulated the expression of Type I interferons and cytokines including IFN-α, IFN-β, IL-6, and TNF-α. It significantly impacted the TLR3 signaling pathways, affecting downstream components such as NF-κB and IRF-3. TLR3 silencing studies indicated that OMT's antiviral efficacy was not solely dependent on the TLR3 pathway. Conclusion Our findings reveal that OMT exhibits a dual-action mechanism by inhibiting H9N2 AIV and modulating immune responses in PMVECs, primarily through the TLR3 signaling pathway. These results lay a promising foundation for the development of OMT as an alternative antiviral therapeutic against H9N2 AIV.

show abstract

“…Despite being classified as low pathogenicity, H9N2 is known for its rapid transmission among poultry, contributing to considerable economic losses and carrying a potential risk of zoonotic transmission [6,7]. The risk it poses is compounded by its robust mutagenic capabilities and gene recombination potential, leading to significant concerns in both veterinary and human medicine and highlighting the critical limitations of current vaccine strategies against rapidly evolving influenza viruses [8,9].…”

Section: Introductionmentioning

confidence: 99%

Oxymatrine Modulation of TLR3 Signaling: A Dual-Action Mechanism for H9N2 Avian Influenza Virus Defense and Immune Regulation

Zhi,

Zhao,

Liu

et al. 2024

Molecules

View full text Add to dashboard Cite

In our research, we explored a natural substance called Oxymatrine, found in a traditional Chinese medicinal plant, to fight against a common bird flu virus known as H9N2. This virus not only affects birds but can also pose a threat to human health. We focused on how this natural compound can help in stopping the virus from spreading in cells that line the lungs of birds and potentially humans. Our findings show that Oxymatrine can both directly block the virus and boost the body’s immune response against it. This dual-action mechanism is particularly interesting because it indicates that Oxymatrine might be a useful tool in developing new ways to prevent and treat this type of bird flu. Understanding how Oxymatrine works against the H9N2 virus could lead to safer and more natural ways to combat viral infections in animals and humans, contributing to the health and well-being of society. The H9N2 Avian Influenza Virus (AIV) is a persistent health threat because of its rapid mutation rate and the limited efficacy of vaccines, underscoring the urgent need for innovative therapies. This study investigated the H9N2 AIV antiviral properties of Oxymatrine (OMT), a compound derived from traditional Chinese medicine, particularly focusing on its interaction with pulmonary microvascular endothelial cells (PMVECs). Employing an array of in vitro assays, including 50% tissue culture infectious dose, Cell Counting Kit-8, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot, we systematically elucidated the multifaceted effects of OMT. OMT dose-dependently inhibited critical antiviral proteins (PKR and Mx1) and modulated the expression of type I interferons and key cytokines (IFN-α, IFN-β, IL-6, and TNF-α), thereby affecting TLR3 signaling and its downstream elements (NF-κB and IRF-3). OMT’s antiviral efficacy extended beyond TLR3-mediated responses, suggesting its potential as a versatile antiviral agent. This study not only contributes to the growing body of research on the use of natural compounds as antiviral agents but also underscores the importance of further investigating the broader application of OMT for combating viral infections.

show abstract

The emergence of new antigen branches of H9N2 avian influenza virus in China due to antigenic drift on hemagglutinin through antibody escape at immunodominant sites

Cited by 19 publications

References 51 publications

Hemagglutinin glycosylation pattern-specific effects: implications for the fitness of H9.4.2.5-branched H9N2 avian influenza viruses

Hemagglutinin glycosylation pattern-specific effects: implications for the fitness of H9.4.2.5-branched H9N2 avian influenza viruses

Oxymatrine Modulation of TLR3 Signaling Pathway: A Dual-Action Mechanism against H9N2 Avian Influenza Virus and Immune Regulation

Oxymatrine Modulation of TLR3 Signaling: A Dual-Action Mechanism for H9N2 Avian Influenza Virus Defense and Immune Regulation

Contact Info

Product

Resources

About