Biogenesis of Influenza A Virus Hemagglutinin Cross-Protective Stem Epitopes

English version České info

Extensive variation in the IAV HA globular domain severely impedes influenza vaccination. Recent findings demonstrate that StRAbs, specific Abs to the highly conserved stem region of HA, can protect hosts against a broad variety of influenza virus strains. In investigating the binding of StRAbs to HA during its biogenesis in IAV-infected cells, we find that these Abs can bind HA monomers prior to their trimerization in the GC. Binding to HA becomes temperature-dependent, however, as N-linked oligosaccharides mature during transport of trimerized HA through the GC to the cell surface. Our findings support the potential use of monomeric HA stem immunogens to induce broadly neutralizing Abs, but raise the possibility of eventual viral escape from StRAbs, based on structural alterations in the HA that increase steric hindrance of HA stem N-linked glycans on StRAb binding.

Vyšlo v časopise: Biogenesis of Influenza A Virus Hemagglutinin Cross-Protective Stem Epitopes. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004204
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004204

Souhrn

Zdroje

1. ReadingSA, DimmockNJ (2007) Neutralization of animal virus infectivity by antibody. Arch Virol 152 : 1047–1059.

2. WilsonIA, SkehelJJ, WileyDC (1981) Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature 289 : 366–373.

3. CatonAJ, BrownleeGG, YewdellJW, GerhardW (1982) The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell 31 : 417–427.

4. WileyDC, WilsonIA, SkehelJJ (1981) Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289 : 373–378.

5. WrigleyNG, BrownEB, DanielsRS, DouglasAR, SkehelJJ, et al. (1983) Electron microscopy of influenza haemagglutinin-monoclonal antibody complexes. Virology 131 : 308–314.

6. SkehelJJ, StevensDJ, DanielsRS, DouglasAR, KnossowM, et al. (1984) A carbohydrate side chain on hemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody. Proc Natl Acad Sci U S A 81 : 1779–1783.

7. YewdellJW, GerhardW, BächiT (1983) Monoclonal anti-hemagglutinin antibodies detect irreversible antigenic alterations that coincide with the acid activation of influenza virus A/PR/834-mediated hemolysis. J Virol 48 : 239–248.

8. BächiT, GerhardW, YewdellJW (1985) Monoclonal antibodies detect different forms of influenza virus hemagglutinin during viral penetration and biosynthesis. J Virol 55 : 307–313.

9. YewdellJW, YellenA, BächiT (1988) Monoclonal antibodies localize events in the folding, assembly, and intracellular transport of the influenza virus hemagglutinin glycoprotein. Cell 52 : 843–852.

10. CopelandCS, ZimmerKP, WagnerKR, HealeyGA, MellmanI, et al. (1988) Folding, trimerization, and transport are sequential events in the biogenesis of influenza virus hemagglutinin. Cell 53 : 197–209.

11. HanY, DavidA, LiuB, MagadánJG, BenninkJR, et al. (2012) Monitoring cotranslational protein folding in mammalian cells at codon resolution. Proc Natl Acad Sci U S A 109 : 12467–12472.

12. ChenW, HeleniusJ, BraakmanI, HeleniusA (1995) Cotranslational folding and calnexin binding during glycoprotein synthesis. Proceedings of the National Academy of Sciences USA 92 : 6229–6233.

13. GethingMJ, McCammonK, SambrookJ (1986) Expression of wild-type and mutant forms of influenza hemagglutinin: the role of folding in intracellular transport. Cell 46 : 939–950.

14. MagadánJG, KhuranaS, DasSR, FrankGM, StevensJ, et al. (2013) Influenza a virus hemagglutinin trimerization completes monomer folding and antigenicity. J Virol 87 : 9742–9753.

15. VareckováE, MuchaV, CiamporF, BetákováT, RussG (1993) Monoclonal antibodies demonstrate accessible HA2 epitopes in minor subpopulation of native influenza virus haemagglutinin molecules. Archives of Virology 130 : 45–56.

16. StykB, RussG, PolákováK (1979) Antigenic glycopolypeptides HA1 and HA2 of influenza virus haemagglutinin. III. Reactivity with human convalescent sera. Acta Virol 23 : 1–8.

17. SmirnovIA, LipatovAS, OkunoI, Gitel'manAK (1999) [A common antigenic epitope in influenza A virus (H1, H2, H5, H6) hemagglutinin]. Vopr Virusol 44 : 111–115.

18. OkunoY, IsegawaY, SasaoF, UedaS (1993) A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains. Journal of Virology 67 : 2552–2558.

19. KashyapAK, SteelJ, OnerAF, DillonMA, SwaleRE, et al. (2008) Combinatorial antibody libraries from survivors of the Turkish H5N1 avian influenza outbreak reveal virus neutralization strategies. Proc Natl Acad Sci U S A 105 : 5986–5991.

20. ThrosbyM, van den BrinkE, JongeneelenM, PoonLLM, AlardP, et al. (2008) Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM+ memory B cells. PLoS ONE 3: e3942.

21. SuiJ, HwangWC, PerezS, WeiG, AirdD, et al. (2009) Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol 16 : 265–273.

22. CortiD, SuguitanAL, PinnaD, SilacciC, Fernandez-RodriguezBM, et al. (2010) Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine. J Clin Invest 120 : 1663–1673.

23. WrammertJ, KoutsonanosD, LiG-M, EdupugantiS, SuiJ, et al. (2011) Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med 208 : 181–193.

24. ThomsonCA, WangY, JacksonL, OlsonM, WangW, et al. (2012) Pandemic H1N1 influenza infection and vaccination in humans induces cross-protective antibodies that target the hemagglutinin stem. Frontiers in Immunology 3 : 87.

25. WeiC-J, BoyingtonJC, McTamneyPM, KongW-P, PearceMB, et al. (2010) Induction of broadly neutralizing H1N1 influenza antibodies by vaccination. Science 329 : 1060–1064.

26. SteelJ, LowenAC, WangTT, YondolaM, GaoQ, et al. (2010) Influenza virus vaccine based on the conserved hemagglutinin stalk domain. MBio 1: e00018–10.

27. WangTT, TanGS, HaiR, PicaN, PetersenE, et al. (2010) Broadly protective monoclonal antibodies against H3 influenza viruses following sequential immunization with different hemagglutinins. PLoS Pathog 6: e1000796.

28. LiGM, ChiuC, WrammertJ, McCauslandM, AndrewsSF, et al. (2012) Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Proc Natl Acad Sci U S A 109 : 9047–9052.

29. DililloDJ, TanGS, PaleseP, RavetchJV (2014) Broadly neutralizing hemagglutinin stalk-specific antibodies require FcgammaR interactions for protection against influenza virus in vivo. Nat Med 20 : 143–151.

30. EkiertDC, BhabhaG, ElsligerM-A, FriesenRHE, JongeneelenM, et al. (2009) Antibody recognition of a highly conserved influenza virus epitope. Science 324 : 246–251.

31. RussG, BenninkJR, BächiT, YewdellJW (1991) Influenza virus hemagglutinin trimers and monomers maintain distinct biochemical modifications and intracellular distribution in brefeldin A-treated cells. Cell Regul 2 : 549–563.

32. DreyfusC, EkiertDC, WilsonIA (2013) Structure of a classical broadly neutralizing stem antibody in complex with a pandemic H2 influenza virus hemagglutinin. J Virol 87 : 7149–7154.

33. CortiD, VossJ, GamblinSJ, CodoniG, MacagnoA, et al. (2011) A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 333 : 850–856.

34. DreyfusC, LaursenNS, KwaksT, ZuijdgeestD, KhayatR, et al. (2012) Highly conserved protective epitopes on influenza B viruses. Science 337 : 1343–1348.

35. GamblinSJ, HaireLF, RussellRJ, StevensDJ, XiaoB, et al. (2004) The structure and receptor binding properties of the 1918 influenza hemagglutinin. Science 303 : 1838–1842.

36. WhiteheadTA, ChevalierA, SongY, DreyfusC, FleishmanSJ, et al. (2012) Optimization of affinity, specificity and function of designed influenza inhibitors using deep sequencing. Nat Biotechnol 30 : 543–548.

37. YewdellJW, TaylorA, YellenA, CatonA, GerhardW, et al. (1993) Mutations in or near the fusion peptide of the influenza virus hemagglutinin affect an antigenic site in the globular region. J Virol 67 : 933–942.

38. StevensJ, CorperAL, BaslerCF, TaubenbergerJK, PaleseP, et al. (2004) Structure of the Uncleaved Human H1 Hemagglutinin from the Extinct 1918 Influenza Virus. Science 303 : 1866–1870.

39. YewdellJW (2013) To dream the impossible dream: universal influenza vaccination. Curr Opin Virol 3 (3) 316–21.

40. YewdellJW, SpiroDJ, GoldingH, QuillH, MittelmanA, et al. (2013) Getting to the heart of influenza. Sci Transl Med 5 : 191ed198.

41. DasSR, PuigbòP, HensleySE, HurtDE, BenninkJR, et al. (2010) Glycosylation focuses sequence variation in the influenza A virus H1 hemagglutinin globular domain. PLoS Pathog 6: e1001211.

42. BlackburneBP, HayAJ, GoldsteinRA (2008) Changing selective pressure during antigenic changes in human influenza H3. PLoS Pathog 4: e1000058.

43. EgginkD, GoffPH, PaleseP (2014) Guiding the immune response against influenza virus hemagglutinin toward the conserved stalk domain by hyperglycosylation of the globular head domain. J Virol 88 : 699–704.

44. FrancisTJr, DavenportFM, HennessyAV (1953) A serological recapitulation of human infection with different strains of influenza virus. Trans Assoc Am Physicians 66 : 231–239.

45. KrammerF, PaleseP (2013) Influenza virus hemagglutinin stalk-based antibodies and vaccines. Curr Opin Virol 3 (5) 521–30.

46. MillerMS, GardnerTJ, KrammerF, AguadoLC, TortorellaD, et al. (2013) Neutralizing Antibodies Against Previously Encountered Influenza Virus Strains Increase over Time: A Longitudinal Analysis. Sci Transl Med 5 : 198ra107.

47. KrammerF, PicaN, HaiR, MargineI, PaleseP (2013) Chimeric hemagglutinin influenza virus vaccine constructs elicit broadly protective stalk-specific antibodies. J Virol 87 : 6542–6550.

48. KrammerF, MargineI, TanGS, PicaN, KrauseJC, et al. (2012) A carboxy-terminal trimerization domain stabilizes conformational epitopes on the stalk domain of soluble recombinant hemagglutinin substrates. PLoS One 7: e43603.

49. BommakantiG, CitronMP, HeplerRW, CallahanC, HeideckerGJ, et al. (2010) Design of an HA2-based Escherichia coli expressed influenza immunogen that protects mice from pathogenic challenge. Proceedings of the National Academy of Sciences 107 : 13701–13706.

50. BommakantiG, LuX, CitronMP, NajarTA, HeideckerGJ, et al. (2012) Design of Escherichia coli-Expressed Stalk Domain Immunogens of H1N1 Hemagglutinin That Protect Mice from Lethal Challenge. Journal of Virology 86 : 13434–13444.

51. KhuranaS, LovingCL, ManischewitzJ, KingLR, GaugerPC, et al. (2013) Vaccine-Induced Anti-HA2 Antibodies Promote Virus Fusion and Enhance Influenza Virus Respiratory Disease. Sci Transl Med 5 : 200ra114.

52. MonsalvoAC, BatalleJP, LopezMF, KrauseJC, KlemencJ, et al. (2011) Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes. Nat Med 17 : 195–199.

53. DowdKA, JostCA, DurbinAP, WhiteheadSS, PiersonTC (2011) A dynamic landscape for antibody binding modulates antibody-mediated neutralization of West Nile virus. PLoS Pathog 7: e1002111.

54. RuprechtCR, KrarupA, ReynellL, MannAM, BrandenbergOF, et al. (2011) MPER-specific antibodies induce gp120 shedding and irreversibly neutralize HIV-1. J Exp Med 208 : 439–454.

55. TomiyaN, NarangS, LeeYC, BetenbaughMJ (2004) Comparing N-glycan processing in mammalian cell lines to native and engineered lepidopteran insect cell lines. Glycoconj J 21 : 343–360.

56. WangCC, ChenJR, TsengYC, HsuCH, HungYF, et al. (2009) Glycans on influenza hemagglutinin affect receptor binding and immune response. Proc Natl Acad Sci U S A 106 : 18137–18142.

57. ChenJR, YuYH, TsengYC, ChiangWL, ChiangMF, et al. (2014) Vaccination of monoglycosylated hemagglutinin induces cross-strain protection against influenza virus infections. Proc Natl Acad Sci U S A 111 : 2476–2481.

58. WangW, AndersonCM, De FeoCJ, ZhuangM, YangH, et al. (2011) Cross-neutralizing antibodies to pandemic 2009 H1N1 and recent seasonal H1N1 influenza A strains influenced by a mutation in hemagglutinin subunit 2. PLoS Pathog 7: e1002081.

59. LefrancoisL, LylesDS (1982) The interaction of antibody with the major surface glycoprotein of vesicular stomatitis virus. I. Analysis of neutralizing epitopes with monoclonal antibodies. Virology 121 : 157–167.

60. DolanBP, LiL, TakedaK, BenninkJR, YewdellJW (2010) Defective ribosomal products are the major source of antigenic peptides endogenously generated from influenza A virus neuraminidase. J Immunol 184 : 1419–1424.

61. YewdellJW, FrankE, GerhardW (1981) Expression of influenza A virus internal antigens on the surface of infected P815 cells. J Immunol 126 : 1814–1819.

62. MagadánJG, Pérez-VictoriaFJ, SougratR, YeY, StrebelK, et al. (2010) Multilayered mechanism of CD4 downregulation by HIV-1 Vpu involving distinct ER retention and ERAD targeting steps. PLoS Pathog 6: e1000869.