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Complex N -glycans are important for interspecies transmission of H7 influenza A viruses.
- Source :
-
Journal of virology [J Virol] 2024 Apr 16; Vol. 98 (4), pp. e0194123. Date of Electronic Publication: 2024 Mar 12. - Publication Year :
- 2024
-
Abstract
- Influenza A viruses (IAVs) can overcome species barriers by adaptation of the receptor-binding site of the hemagglutinin (HA). To initiate infection, HAs bind to glycan receptors with terminal sialic acids, which are either N -acetylneuraminic acid (NeuAc) or N -glycolylneuraminic acid (NeuGc); the latter is mainly found in horses and pigs but not in birds and humans. We investigated the influence of previously identified equine NeuGc-adapting mutations (S128T, I130V, A135E, T189A, and K193R) in avian H7 IAVs in vitro and in vivo . We observed that these mutations negatively affected viral replication in chicken cells but not in duck cells and positively affected replication in horse cells. In vivo , the mutations reduced virus virulence and mortality in chickens. Ducks excreted high viral loads longer than chickens, although they appeared clinically healthy. To elucidate why these viruses infected chickens and ducks despite the absence of NeuGc, we re-evaluated the receptor binding of H7 HAs using glycan microarray and flow cytometry studies. This re-evaluation demonstrated that mutated avian H7 HAs also bound to α2,3-linked NeuAc and sialyl-LewisX, which have an additional fucose moiety in their terminal epitope, explaining why infection of ducks and chickens was possible. Interestingly, the α2,3-linked NeuAc and sialyl-LewisX epitopes were only bound when presented on tri-antennary N -glycans, emphasizing the importance of investigating the fine receptor specificities of IAVs. In conclusion, the binding of NeuGc-adapted H7 IAV to tri-antennary N -glycans enables viral replication and shedding by chickens and ducks, potentially facilitating interspecies transmission of equine-adapted H7 IAVs.IMPORTANCEInfluenza A viruses (IAVs) cause millions of deaths and illnesses in birds and mammals each year. The viral surface protein hemagglutinin initiates infection by binding to host cell terminal sialic acids. Hemagglutinin adaptations affect the binding affinity to these sialic acids and the potential host species targeted. While avian and human IAVs tend to bind to N -acetylneuraminic acid (sialic acid), equine H7 viruses prefer binding to N -glycolylneuraminic acid (NeuGc). To better understand the function of NeuGc-specific adaptations in hemagglutinin and to elucidate interspecies transmission potential NeuGc-adapted viruses, we evaluated the effects of NeuGc-specific mutations in avian H7 viruses in chickens and ducks, important economic hosts and reservoir birds, respectively. We also examined the impact on viral replication and found a binding affinity to tri-antennary N -glycans containing different terminal epitopes. These findings are significant as they contribute to the understanding of the role of receptor binding in avian influenza infection.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- Animals
Humans
Epitopes chemistry
Epitopes metabolism
Hemagglutinin Glycoproteins, Influenza Virus chemistry
Hemagglutinin Glycoproteins, Influenza Virus genetics
Hemagglutinin Glycoproteins, Influenza Virus metabolism
Mutation
N-Acetylneuraminic Acid chemistry
N-Acetylneuraminic Acid metabolism
Receptors, Virus chemistry
Receptors, Virus genetics
Receptors, Virus metabolism
Swine virology
Viral Zoonoses metabolism
Viral Zoonoses transmission
Viral Zoonoses virology
Chickens genetics
Chickens metabolism
Chickens virology
Ducks genetics
Ducks metabolism
Ducks virology
Horses genetics
Horses metabolism
Horses virology
Influenza A virus chemistry
Influenza A virus classification
Influenza A virus metabolism
Influenza in Birds genetics
Influenza in Birds transmission
Influenza in Birds virology
Neuraminic Acids chemistry
Neuraminic Acids metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 98
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 38470143
- Full Text :
- https://doi.org/10.1128/jvi.01941-23