甲型流感病毒表面糖基化与疫苗设计
Influenza A surface glycosylation and vaccine design.
作者信息
Wu Chung-Yi, Lin Chih-Wei, Tsai Tsung-I, Lee Chang-Chun David, Chuang Hong-Yang, Chen Jhih-Bin, Tsai Ming-Hung, Chen Bo-Rui, Lo Pei-Wen, Liu Chiu-Ping, Shivatare Vidya S, Wong Chi-Huey
机构信息
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan
出版信息
Proc Natl Acad Sci U S A. 2017 Jan 10;114(2):280-285. doi: 10.1073/pnas.1617174114. Epub 2016 Dec 27.
Abstract
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 IAV-specific CD8 T-cell response and a strong cross-strain as well as cross-subtype protection against various virus strains.
摘要
我们已经表明，甲型流感病毒（IAV）血凝素（HA）的糖基化，尤其是在N-27位的糖基化，对于HA折叠和病毒存活至关重要。然而，尚不清楚HA以及IAV的其他两种主要表面糖蛋白神经氨酸酶（NA）和M2离子通道的糖基化对于IAV复制是否必不可少。在此，我们表明HA在N-142位的糖基化调节病毒感染性和宿主免疫反应。NA茎区的糖基化影响其结构、活性和特异性，从而调节病毒释放和毒力，而催化结构域的糖基化影响其热稳定性；然而，M2的糖基化对其功能没有影响。此外，使用不含NA茎区和催化结构域的IAV作为减毒活疫苗，已显示可赋予强烈的IAV特异性CD8 T细胞反应以及针对各种病毒株的强大的交叉株和交叉亚型保护。
相似文献
1
Influenza A surface glycosylation and vaccine design.甲型流感病毒表面糖基化与疫苗设计
Proc Natl Acad Sci U S A. 2017 Jan 10;114(2):280-285. doi: 10.1073/pnas.1617174114. Epub 2016 Dec 27.
2
A Bivalent Heterologous DNA Virus-Like-Particle Prime-Boost Vaccine Elicits Broad Protection against both Group 1 and 2 Influenza A Viruses.一种二价异源DNA病毒样颗粒初免-加强疫苗可引发针对1型和2型甲型流感病毒的广泛保护。
J Virol. 2017 Apr 13;91(9). doi: 10.1128/JVI.02052-16. Print 2017 May 1.
3
A recombinant H7N9 influenza vaccine with the H7 hemagglutinin transmembrane domain replaced by the H3 domain induces increased cross-reactive antibodies and improved interclade protection in mice.一种将H7血凝素跨膜结构域替换为H3结构域的重组H7N9流感疫苗可诱导小鼠产生更多的交叉反应抗体，并增强不同进化枝间的保护作用。
Antiviral Res. 2017 Jul;143:97-105. doi: 10.1016/j.antiviral.2017.03.029. Epub 2017 Apr 10.
4
Immunogenicity and efficacy of replication-competent recombinant influenza virus carrying multimeric M2 extracellular domains in a chimeric hemagglutinin conjugate.携带嵌合血凝素缀合物的多聚体 M2 细胞外结构域的复制型重组流感病毒的免疫原性和功效。
Antiviral Res. 2017 Dec;148:43-52. doi: 10.1016/j.antiviral.2017.10.018. Epub 2017 Oct 26.
5
Evaluation of the immunogenicity and protective effects of a trivalent chimeric norovirus P particle immunogen displaying influenza HA2 from subtypes H1, H3 and B.对展示来自H1、H3和B亚型流感HA2的三价嵌合诺如病毒P颗粒免疫原的免疫原性和保护作用的评估。
Emerg Microbes Infect. 2016 May 25;5(5):e51. doi: 10.1038/emi.2016.51.
6
A replication-incompetent virus possessing an uncleavable hemagglutinin as an influenza vaccine.一种复制缺陷型病毒，具有不可切割的血凝素，可用作流感疫苗。
Vaccine. 2012 Sep 14;30(42):6027-33. doi: 10.1016/j.vaccine.2012.07.059. Epub 2012 Aug 3.
7
Intranasal delivery of a cDC1 targeted influenza vaccine with poly(I:C) enhances T cell responses and protects against influenza infection.鼻内递送靶向树突状细胞的流感疫苗与聚肌苷酸：胞苷酸增强 T 细胞反应并预防流感感染。
Scand J Immunol. 2022 Mar;95(3):e13128. doi: 10.1111/sji.13128. Epub 2021 Dec 27.
8
Roles of antibodies to influenza A virus hemagglutinin, neuraminidase, and M2e in conferring cross protection.甲型流感病毒血凝素、神经氨酸酶及基质蛋白2外显子抗体在提供交叉保护中的作用。
Biochem Biophys Res Commun. 2017 Nov 4;493(1):393-398. doi: 10.1016/j.bbrc.2017.09.011. Epub 2017 Sep 5.
9
Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus Increases Its Virulence in Mice by Exacerbating the Host Immune Response.H5N1流感病毒血凝素蛋白的糖基化通过加剧宿主免疫反应增强其在小鼠中的毒力。
J Virol. 2017 Mar 13;91(7). doi: 10.1128/JVI.02215-16. Print 2017 Apr 1.
10
Potency of an inactivated influenza vaccine prepared from A/duck/Hong Kong/960/1980 (H6N2) against a challenge with A/duck/Vietnam/OIE-0033/2012 (H6N2) in mice.由A/鸭/香港/960/1980（H6N2）制备的灭活流感疫苗对小鼠感染A/鸭/越南/OIE - 0033/2012（H6N2）的效力。
Arch Virol. 2014 Oct;159(10):2567-74. doi: 10.1007/s00705-014-2107-2. Epub 2014 May 14.
引用本文的文献
1
SUMOylation of SARS-CoV-2 spike protein is a key target for broad-spectrum antiviral therapy.严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白的类泛素化修饰是广谱抗病毒治疗的关键靶点。
Theranostics. 2025 May 25;15(13):6369-6386. doi: 10.7150/thno.111256. eCollection 2025.
2
H3 hemagglutinin proteins optimized for 2018 to 2022 elicit neutralizing antibodies across panels of modern influenza A(H3N2) viruses.针对2018年至2022年优化的H3血凝素蛋白可引发针对多种现代甲型H3N2流感病毒的中和抗体。
J Immunol. 2025 Jul 1;214(7):1698-1713. doi: 10.1093/jimmun/vkaf092.
3
Making Universal Vaccines and Antibodies Through Glycoengineering.通过糖基工程制备通用疫苗和抗体。
Methods Mol Biol. 2025;2926:35-50. doi: 10.1007/978-1-0716-4542-0_3.
4
Computational design of a glycosylated multi-epitope vaccine against HAsV-1 and HAsV-2 astrovirus for acute gastroenteritis.针对甲型星状病毒1型和2型引起的急性肠胃炎的糖基化多表位疫苗的计算设计。
Sci Rep. 2025 Apr 22;15(1):13954. doi: 10.1038/s41598-025-96989-2.
5
PROTAR Vaccine 2.0 generates influenza vaccines by degrading multiple viral proteins.PROTAR疫苗2.0通过降解多种病毒蛋白来生产流感疫苗。
Nat Chem Biol. 2025 Jan 15. doi: 10.1038/s41589-024-01813-z.
6
Development of Glycan-masked SARS-CoV-2 RBD vaccines against SARS-related coronaviruses.糖基掩蔽 SARS-CoV-2 RBD 疫苗的开发用于对抗 SARS 相关冠状病毒。
PLoS Pathog. 2024 Sep 26;20(9):e1012599. doi: 10.1371/journal.ppat.1012599. eCollection 2024 Sep.
7
Isolation and characterization of IgG3 glycan-targeting antibodies with exceptional cross-reactivity for diverse viral families.分离和鉴定对多种病毒家族具有异常交叉反应性的 IgG3 聚糖靶向抗体。
PLoS Pathog. 2024 Sep 18;20(9):e1012499. doi: 10.1371/journal.ppat.1012499. eCollection 2024 Sep.
8
Molecular Markers and Mechanisms of Influenza A Virus Cross-Species Transmission and New Host Adaptation.甲型流感病毒跨种传播和新宿主适应的分子标志物和机制。
Viruses. 2024 May 30;16(6):883. doi: 10.3390/v16060883.
9
Anti-neuraminidase immunity in the combat against influenza.抗神经氨酸酶免疫在抗击流感中的作用。
Expert Rev Vaccines. 2024 Jan-Dec;23(1):474-484. doi: 10.1080/14760584.2024.2343689. Epub 2024 Apr 23.
10
Low-sugar universal mRNA vaccine against coronavirus variants with deletion of glycosites in the S2 or stem of SARS-CoV-2 spike messenger RNA (mRNA).针对冠状病毒变体的低糖通用 mRNA 疫苗，该疫苗在 SARS-CoV-2 刺突信使 RNA（mRNA）的 S2 或茎中删除了糖基化位点。
Proc Natl Acad Sci U S A. 2023 Dec 5;120(49):e2314392120. doi: 10.1073/pnas.2314392120. Epub 2023 Nov 27.
本文引用的文献
1
A Novel Vaccination Strategy Mediating the Induction of Lung-Resident Memory CD8 T Cells Confers Heterosubtypic Immunity against Future Pandemic Influenza Virus.一种介导肺驻留记忆性CD8 T细胞诱导的新型疫苗接种策略赋予针对未来大流行性流感病毒的异源亚型免疫力。
J Immunol. 2016 Mar 15;196(6):2637-45. doi: 10.4049/jimmunol.1501637. Epub 2016 Feb 10.
2
Age Dependence and Isotype Specificity of Influenza Virus Hemagglutinin Stalk-Reactive Antibodies in Humans.人类流感病毒血凝素茎部反应性抗体的年龄依赖性和亚型特异性
mBio. 2016 Jan 19;7(1):e01996-15. doi: 10.1128/mBio.01996-15.
3
Strategies towards universal pandemic influenza vaccines.通用大流行性流感疫苗的策略。
Expert Rev Vaccines. 2016;15(2):215-25. doi: 10.1586/14760584.2016.1115352. Epub 2015 Dec 5.
4
Differential Recognition of Influenza A Viruses by M158-66 Epitope-Specific CD8+ T Cells Is Determined by Extraepitopic Amino Acid Residues.M158 - 66表位特异性CD8 + T细胞对甲型流感病毒的差异识别由表位外氨基酸残基决定。
J Virol. 2015 Nov 4;90(2):1009-22. doi: 10.1128/JVI.02439-15. Print 2016 Jan 15.
5
Endogenous antigen processing drives the primary CD4+ T cell response to influenza.内源性抗原加工驱动了针对流感的初始CD4+T细胞反应。
Nat Med. 2015 Oct;21(10):1216-22. doi: 10.1038/nm.3958. Epub 2015 Sep 28.
6
A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen.稳定的三聚体流感血凝素茎作为一种广泛保护性的免疫原。
Science. 2015 Sep 18;349(6254):1301-6. doi: 10.1126/science.aac7263. Epub 2015 Aug 24.
7
The Mechanism by which 146-N-Glycan Affects the Active Site of Neuraminidase.146-N-聚糖影响神经氨酸酶活性位点的机制。
PLoS One. 2015 Aug 12;10(8):e0135487. doi: 10.1371/journal.pone.0135487. eCollection 2015.
8
Viral subpopulation diversity in influenza virus isolates compared to clinical specimens.与临床样本相比，流感病毒分离株中的病毒亚群多样性。
J Clin Virol. 2015 Jul;68:16-23. doi: 10.1016/j.jcv.2015.04.010. Epub 2015 Apr 11.
9
Antibody to Influenza Virus Neuraminidase: An Independent Correlate of Protection.抗流感病毒神经氨酸酶抗体：保护作用的独立相关因素。
J Infect Dis. 2015 Oct 15;212(8):1191-9. doi: 10.1093/infdis/jiv195. Epub 2015 Apr 8.
10
Structure and receptor binding preferences of recombinant hemagglutinins from avian and human H6 and H10 influenza A virus subtypes.来自甲型禽流感病毒H6和H10亚型的重组血凝素的结构及受体结合偏好性
J Virol. 2015 Apr;89(8):4612-23. doi: 10.1128/JVI.03456-14. Epub 2015 Feb 11.
Zotero 插件