Complex N-glycans are important for interspecies transmission of H7 influenza A viruses
文献类型：期刊论文
| 作者 | Spruit, Cindy M.4; Palme, Diana I.3; Li, Tiehai2,5; Rios Carrasco, Maria4; Gabarroca Garcia, Alba4; Sweet, Igor R.4; Kuryshko, Maryna3; Maliepaard, Joshua C. L.1,6; Reiding, Karli R.1,6; Scheibner, David3 |
| 刊名 | JOURNAL OF VIROLOGY
 |
| 出版日期 | 2024-03-12 |
| 页码 | 21 |
| 关键词 | influenza A virus hemagglutinin interspecies transmission sialyl-LewisX NeuGc |
| ISSN号 | 0022-538X |
| DOI | 10.1128/jvi.01941-23 |
| 通讯作者 | Abdelwhab, Elsayed M.(sayed.abdel-whab@fli.de) ; de Vries, Robert P.(r.vries@uu.nl) |
| 英文摘要 | 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 alpha 2,3-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 alpha 2,3-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. IMPORTANCE Influenza 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. |
| WOS关键词 | RECEPTOR-BINDING SPECIFICITY ; HEMAGGLUTININ ; ACID ; GLYCOSYLATION ; STABILITY ; EVOLUTION ; PROFILES ; ECOLOGY |
| 资助项目 | EC | Horizon 2020 Framework Programme (H2020) |
| WOS研究方向 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:001183384700001 |
| 出版者 | AMER SOC MICROBIOLOGY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/310517]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Abdelwhab, Elsayed M.; de Vries, Robert P. |
| 作者单位 | 1.Univ Utrecht, Bijvoet Ctr Biomol Res, Biomol Mass Spectrometry & Prote, Utrecht, Netherlands 2.Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA USA 3.Friedrich Loeffler Inst, Inst Mol Virol & Cell Biol, Fed Res Inst Anim Hlth, Greifswald, Germany 4.Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Chem Biol & Drug Discovery, Utrecht, Netherlands 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 6.Univ Utrecht, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands |
| 推荐引用方式 GB/T 7714 | Spruit, Cindy M.,Palme, Diana I.,Li, Tiehai,et al. Complex N-glycans are important for interspecies transmission of H7 influenza A viruses[J]. JOURNAL OF VIROLOGY,2024:21. |
| APA | Spruit, Cindy M..,Palme, Diana I..,Li, Tiehai.,Rios Carrasco, Maria.,Gabarroca Garcia, Alba.,...&de Vries, Robert P..(2024).Complex N-glycans are important for interspecies transmission of H7 influenza A viruses.JOURNAL OF VIROLOGY,21. |
| MLA | Spruit, Cindy M.,et al."Complex N-glycans are important for interspecies transmission of H7 influenza A viruses".JOURNAL OF VIROLOGY (2024):21. |
入库方式： OAI收割
来源：上海药物研究所
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