Hemagglutinin glycosylation modulates the pathogenicity and antigenicity of the H5N1 avian influenza virus

Zhang, Xiaojian; Chen, Sujuan; Jiang, Yi; Huang, Kai; Huang, Jun; Yang, Da; Zhu, Jingjing; Zhu, Yinbiao; Shi, Suhua; Peng, Daxin; Liu, Xiufan

doi:10.1016/j.vetmic.2014.12.011

Cited by 48 publications

(48 citation statements)

References 54 publications

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“…In addition, the presence or absence of NLG at this residue can affect viral antigenicity and pathogenicity, in conjunction with nearby NLG sites44. Consistent with a previous observation44, we obtained an approximately 10-fold increase of viral replication following this HA mutation (Fig. 2).…”

Section: Discussionsupporting

confidence: 91%

Single PA mutation as a high yield determinant of avian influenza vaccines

Lee

Kim

Park

et al. 2017

Sci Rep

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Human infection with an avian influenza virus persists. To prepare for a potential outbreak of avian influenza, we constructed a candidate vaccine virus (CVV) containing hemagglutinin (HA) and neuraminidase (NA) genes of a H5N1 virus and evaluated its antigenic stability after serial passaging in embryonated chicken eggs. The passaged CVV harbored the four amino acid mutations (R136K in PB2; E31K in PA; A172T in HA; and R80Q in M2) without changing its antigenicity, compared with the parental CVV. Notably, the passaged CVV exhibited much greater replication property both in eggs and in Madin-Darby canine kidney and Vero cells. Of the four mutations, the PA E31K showed the greatest effect on the replication property of reverse genetically-rescued viruses. In a further luciferase reporter, mini-replicon assay, the PA mutation appeared to affect the replication property by increasing viral polymerase activity. When applied to different avian influenza CVVs (H7N9 and H9N2 subtypes), the PA E31K mutation resulted in the increases of viral replication in the Vero cell again. Taken all together, our results suggest the PA E31K mutation as a single, substantial growth determinant of avian influenza CVVs and for the establishment of a high-yield avian influenza vaccine backbone.

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Section: Discussionsupporting

confidence: 91%

Single PA mutation as a high yield determinant of avian influenza vaccines

Lee

Kim

Park

et al. 2017

Sci Rep

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“…H5N1 viruses lacking glycosylation at N158 transmit efficiently by direct contact among guinea-pigs [62]. In 2015, Zhang et al [63] examined the impact of glycosylation at three sites in the HA1 of an H5N1 virus (A/Mallard/Huadong/S/2005) and reached the conclusions that loss of glycosylation at N158 was a prerequisite for binding to α2,6-modified RBCs, and viruses with a loss of glycosylation at N158 or N169 had higher lethality in mice. In 2010, Liao et al [64 •• ] showed that deletion of glycosylation sites in an H5 derived from a consensus-based sequence [65] led to no major change in the glycan binding profiles for α2-3 oligosaccharides.…”

Section: Impact Of Ha Glycosylation On Specificitymentioning

confidence: 99%

New insights into influenza A specificity: an evolution of paradigms

White

Hadden

et al. 2017

Current Opinion in Structural Biology

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Understanding the molecular origin of influenza receptor specificity is complicated by the paucity of quantitative affinity measurements, and the qualitative and variable nature of glycan array data. Further obstacles arise from the varied impact of viral glycosylation and the relatively narrow spectrum of biologically relevant receptors present on glycan arrays. A survey of receptor conformational properties is presented, leading to the conclusion that conformational entropy plays a key role in defining specificity, as does the newly reported ability of biantennary receptors that terminate in Siaα2-6Gal sequences to form bidentate interactions to two binding sites in a hemagglutinin trimer. Bidentate binding provides a functional explanation for the observation that Siaα2-6 receptors adopt an open-umbrella topology when bound to hemagglutinins from human-infective viruses, and calls for a reassessment of virus avidity and tissue tropism.

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“…It was shown that the N -glycosylation of the influenza hemagglutinin plays an important role in the life cycle of influenza virus and influences its antigenic fitness. Indeed, oligosaccharides attached to the globular head of HA were shown to modulate virus antigenic properties (8–10) and its receptor binding (11, 12). The oligosaccharides attached to the stem region were suggested to play a critical role in HA cleavage, replication, and pH stability (13–15).…”

Section: Introductionmentioning

confidence: 99%

The Length of N-Glycans of Recombinant H5N1 Hemagglutinin Influences the Oligomerization and Immunogenicity of Vaccine Antigen

et al. 2017

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Hemagglutinin glycoprotein (HA) is a principle influenza vaccine antigen. Recombinant HA-based vaccines become a potential alternative for traditional approach. Complexity and variation of HA N-glycosylation are considered as the important factors for the vaccine design. The number and location of glycan moieties in the HA molecule are also crucial. Therefore, we decided to study the effect of N-glycosylation pattern on the H5 antigen structure and its ability to induce immunological response. We also decided to change neither the number nor the position of the HA glycosylation sites but only the glycan length. Two variants of the H5 antigen with high mannose glycosylation (H5hm) and with low-mannose glycosylation (H5Man5) were prepared utilizing different Pichia strains. Our structural studies demonstrated that only the highly glycosylated H5 antigen formed high molecular weight oligomers similar to viral particles. Further, the H5hm was much more immunogenic for mice than H5Man5. In summary, our results suggest that high mannose glycosylation of vaccine antigen is superior to the low glycosylation pattern. Our findings have strong implications for the recombinant HA-based influenza vaccine design.

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Hemagglutinin glycosylation modulates the pathogenicity and antigenicity of the H5N1 avian influenza virus

Cited by 48 publications

References 54 publications

Single PA mutation as a high yield determinant of avian influenza vaccines

Single PA mutation as a high yield determinant of avian influenza vaccines

New insights into influenza A specificity: an evolution of paradigms

The Length of N-Glycans of Recombinant H5N1 Hemagglutinin Influences the Oligomerization and Immunogenicity of Vaccine Antigen

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