The Universal Epitope of Influenza A Viral Neuraminidase Fundamentally Contributes to Enzyme Activity and Viral Replication

Doyle, Tracey M.; Jaentschke, Bozena; Domselaar, Gary Van; Hashem, Anwar M.; Farnsworth, Aaron; Forbes, Nicole; Li, Changgui; Wang, Junzhi; He, Runtao; Brown, Earl G.; Li, Xuguang

doi:10.1074/jbc.m113.468884

Cited by 27 publications

(23 citation statements)

References 43 publications

(36 reference statements)

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“…8A). A conserved NA epitope that is recognized by HCA-2 under denaturing conditions (65,66) and localized within the NA catalytic site, and the amino acids necessary for binding a recently reported set of MAbs that recognize H1N1 and H5N1 NA (67) do not overlap this N1-5-VHHm escape mutation (Fig. 8A).…”

Section: N1-3-vhhb and N1-3-vhh-fc Protect Against A Challenge With Omentioning

confidence: 88%

Single-Domain Antibodies Targeting Neuraminidase Protect against an H5N1 Influenza Virus Challenge

Cardoso

Ibáñez

Hoecke

et al. 2014

J Virol

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Section: N1-3-vhhb and N1-3-vhh-fc Protect Against A Challenge With Omentioning

confidence: 88%

Single-Domain Antibodies Targeting Neuraminidase Protect against an H5N1 Influenza Virus Challenge

Cardoso

Ibáñez

Hoecke

et al. 2014

J Virol

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“…Another research team reported that N1 conserved epitopes at NA residues 273, 338, and 339 induced cross-reactive NA-specific antibodies and provided protection against seasonal H1N1, 1918 H1N1, 2009 pandemic H1N1 (pH1N1), and H5N1 avian influenza viruses (34). To date, the only NA epitopes that are universally conserved among all influenza A viruses have been reported at NA residues 222 to 230 for the formation of active sites at residues 224 and 227 (␤ 3 L 01 ) (36). In the present study, we found four amino acid residues close to active enzyme sites in pH1N1 (A/Texas/05/2009) and H5N1 (A/Vietnam/1203/2004): I149V, N344Y, I365T, and S366N (Fig.…”

Section: Discussionmentioning

confidence: 99%

Cross-Reactive Neuraminidase-Inhibiting Antibodies Elicited by Immunization with Recombinant Neuraminidase Proteins of H5N1 and Pandemic H1N1 Influenza A Viruses

Liu

Lin

Tsou

et al. 2015

J Virol

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“…The other major glycoprotein of IAV, NA, is involved in the cleavage of SA on the host cell receptor to facilitate the release of viral particles to infect other cells (4). M2, the third surface protein of IAV, has ion channel activity to regulate virus penetration and uncoating (1).…”

mentioning

confidence: 99%

Influenza A surface glycosylation and vaccine design

Lin

Tsai

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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We have shown that glycosylation of influenza A virus (IAV) hemagglutinin (HA), especially at position N-27, is crucial for HA folding and virus survival. However, it is not known whether the glycosylation of HA and the other two major IAV surface glycoproteins, neuraminidase (NA) and M2 ion channel, is essential for the replication of IAV. Here, we show that glycosylation of HA at N-142 modulates virus infectivity and host immune response. Glycosylation of NA in the stalk region affects its structure, activity, and specificity, thereby modulating virus release and virulence, and glycosylation at the catalytic domain affects its thermostability; however, glycosylation of M2 had no effect on its function. In addition, using IAV without the stalk and catalytic domains of NA as a live attenuated vaccine was shown to confer a strong IAVspecific CD8+ T-cell response and a strong cross-strain as well as cross-subtype protection against various virus strains.influenza A virus | glycosylation | vaccine design I nfluenza A viruses (IAV) belong to the Orthomyxoviridae family and can circulate widely and cross interspecies barriers through the highly antigenic drift and shift of the 18 subtypes of HA and 11 subtypes of neuraminidase (NA) (1, 2). In addition, the posttranslational modification of the IAV surface proteins is important to circumvent host defense and support the virus life cycle (3).HA is a major surface glycoprotein of IAV and is involved in viral infection via binding to sialic acid (SA)-containing glycans on the surface of host cell (3). The other major glycoprotein of IAV, NA, is involved in the cleavage of SA on the host cell receptor to facilitate the release of viral particles to infect other cells (4). M2, the third surface protein of IAV, has ion channel activity to regulate virus penetration and uncoating (1). All surface proteins interact with M1 protein for virus assembly and release (5).The modification of HA and NA by N-glycosylation is important in the IAV life cycle (1, 6-8). Previously, we have shown that the glycosylation of HA affects its receptor binding, immune response, and structural stability, and glycosite 27 is essential for retaining the structural integrity of HA and its receptor binding (6, 9). In addition, using the monoglycosylated HA as immunogen, it showed a broader protection against various IAV subtypes compared with the fully glycosylated version (10). However, it is not clear whether the other specific glycosites and their glycan structures on HA regulate its functions. With regard to NA, the functional roles of its glycosylation are not well understood, though N-glycosylation was reported to stabilize the protein from protease digestion and may affect the enzyme activity (11,12). The aim of this study was to understand the functional effects of glycosylation on HA, NA, and M2, and how glycosylation of the surface proteins affects the life cycle of IAV. ResultsGlycosylation of HA at N-142. Because several glycosylation sites (glycosites 27, 40, 176, 303, and 497) on HA are ...

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The Universal Epitope of Influenza A Viral Neuraminidase Fundamentally Contributes to Enzyme Activity and Viral Replication

Cited by 27 publications

References 43 publications

Single-Domain Antibodies Targeting Neuraminidase Protect against an H5N1 Influenza Virus Challenge

Single-Domain Antibodies Targeting Neuraminidase Protect against an H5N1 Influenza Virus Challenge

Cross-Reactive Neuraminidase-Inhibiting Antibodies Elicited by Immunization with Recombinant Neuraminidase Proteins of H5N1 and Pandemic H1N1 Influenza A Viruses

Influenza A surface glycosylation and vaccine design

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