Identification and characterization of a novel antigenic epitope in the hemagglutinin of the escape mutants of H9N2 avian influenza viruses

Zhu, Yinbiao; Yang, Da; Ren, Qian; Yang, Yang; Liu, Xin; Xu, Xiulong; Liu, Wei; Chen, Sujuan; Peng, Daxin; Liu, Xiufan

doi:10.1016/j.vetmic.2015.04.012

Cited by 37 publications

(45 citation statements)

References 21 publications

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“…Although these residues were important for the binding of murine mAbs, their significance in the context of circulating field viruses remained unknown. Many residues identified in our previous study, as well as several similar published studies [26][27][28][29][30] , are completely conserved amongst circulating viruses indicating they are not responsible for antigenic variability observed in the field.…”

Section: Introductionsupporting

confidence: 59%

“…Six studies describe a total of 39 unique mAb escape mutations in H9N2 HA1 across 30 amino acid positions [25][26][27][28][29][30] (Table S1). Viruses were generated with mutations at each published escape residue in the HA of the H9N2 virus A/chicken/Pakistan/UDL-01/2008 (UDL1/08) and tested using HI, with a panel of 8 anti-UDL1/08 chicken post-infection antisera, to assess the impact of these mutations on antigenicity.…”

Section: Antigenic Impact Of Escape Mutant Virusesmentioning

confidence: 99%

“…In this paper, we identify amino acid residues and substitutions responsible for H9N2 virus antigenic variability in the field through a variety of approaches. We reconstitute mutations at every published H9 HA monoclonal escape mutant position [25][26][27][28][29][30] and test the effect of these substitutions on polyclonal chicken antisera binding. We then adapt an approach previously developed for human influenza viruses 17 , performing a meta-analysis of all published H9 HI assay and corresponding genetic data to identify naturally-occurring antigenically-important substitutions.…”

Section: Introductionmentioning

confidence: 99%

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The molecular basis of antigenic variation among A(H9N2) avian influenza viruses

Peacock

Harvey

Sadeyen

et al. 2018

Preprint

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Avian influenza A(H9N2) viruses are an increasing threat to global poultry production and, through zoonotic infection, to human health where they are considered viruses with pandemic potential. Vaccination of poultry is a key element of disease control in endemic countries, but vaccine effectiveness is persistently challenged by the emergence of antigenic variants. Here we employed a combination of techniques to investigate the genetic basis of H9N2 antigenic variability and evaluate the role of different molecular mechanisms of immune escape. We systematically tested the influence of published H9N2 monoclonal antibody escape mutants on chicken antisera binding, determining that many have no significant effect. Substitutions introducing additional glycosylation sites were a notable exception, though these are relatively rare among circulating viruses. To identify substitutions responsible for antigenic variation in circulating viruses, we performed an integrated meta-analysis of all published H9 haemagglutinin sequences and antigenic data. We validated this statistical analysis experimentally and allocated several new residues to H9N2 antigenic sites providing molecular markers that will help explain vaccine breakdown in the field and inform vaccine selection decisions. We find evidence for the importance of alternative mechanisms of immune escape, beyond simple modulation of epitope structure, with substitutions increasing glycosylation or receptor-binding avidity exhibiting the largest impacts on chicken antisera binding. Of these, meta-analysis indicates avidity regulation to be more relevant to the evolution of circulating viruses, suggesting that a specific focus on avidity regulation is required to fully understand the molecular basis of immune escape by influenza, and potentially other viruses.

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Section: Introductionsupporting

confidence: 59%

Section: Antigenic Impact Of Escape Mutant Virusesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The molecular basis of antigenic variation among A(H9N2) avian influenza viruses

Peacock

Harvey

Sadeyen

et al. 2018

Preprint

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“…H9N2 AIVs A/chicken/Shanghai/F/98 (F98) and A/chicken/ Taixing/10/2010 (TX) (Zhu et al, 2015a,b) were propagated in 10-day-old specific-pathogen-free (SPF) embryonated chicken eggs. The allantoic fluids containing virus were harvested and stored at -70°C.…”

Section: Methodsmentioning

confidence: 99%

Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses

et al. 2017

Self Cite

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H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128) were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.

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“…As shown in Table , the amino acid sequences at the cleavage sites of the HA protein represented the low pathogenicity feature. Notably, at the receptor binding sites (H9 numbering), all isolated H9N2 viruses possessed leucine (L) at position 234, which was reported to contribute to the human‐type receptor binding of the H9N2 virus, and glycine (G) at position 236 also displaying human virus‐like cell tropisms . According to results predicted by NetNGlyc 1.0 Server, all 17 Jiangxi isolates possessed 8 N‐linked potential glycosylation sites in the HA protein at positions (29, 141, 218, 298, 305, 313, 492, and 551).…”

Section: Resultsmentioning

confidence: 93%

The evolution and molecular characteristics of H9N2 avian influenza viruses in Jiangxi of China

Han

Yan

et al. 2018

Journal of Medical Virology

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To understand the evolution and molecular characteristics of Jiangxi H9N2 viruses, we isolated 17 viruses in 2011 and analyzed their characteristics. Phylogenetic analyses revealed that their hemagglutinin genes originate from JS/1/00‐like sublineage, neuraminidase genes originate from BJ/94‐like sublineage, PB1, PA, NP, and NS genes all come from SH/F/98‐like sublineage, PB2 genes originate from ST/163/04‐like sublineage, while M genes come from G1‐like sublineage. Genotype analysis showed that our isolates were classified as genotype 57. Molecular analyses indicated that our strains contained specific sites characteristic of low‐pathogenic viruses. The current study once again highlights the necessity for continued surveillance of novel H9N2 viruses.

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Identification and characterization of a novel antigenic epitope in the hemagglutinin of the escape mutants of H9N2 avian influenza viruses

Cited by 37 publications

References 21 publications

The molecular basis of antigenic variation among A(H9N2) avian influenza viruses

The molecular basis of antigenic variation among A(H9N2) avian influenza viruses

Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses

The evolution and molecular characteristics of H9N2 avian influenza viruses in Jiangxi of China

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