Diverse Heterologous Primary Infections Radically Alter Immunodominance Hierarchies and Clinical Outcomes Following H7N9 Influenza Challenge in Mice

English version České info

The emergence of human infections with a novel strain of avian-origin H7N9 virus in China raises a pandemic concern. The introduction of a new subtype in humans makes people at all ages susceptible due to the lack of population-wide neutralizing antibodies. However, cross-subtype protection from existing host immunity might provide important protection that can limit severe disease. Our study found that previous infection with non-H7N9 subtype viruses such as H9N2 viruses or H1N1 viruses could provide protection against lethal H7N9 challenge to varying degrees in mice. The virus-specific memory CD8+ T cells generated by the previous infection but targeting conserved or related portions of the internal proteins (epitopes) of the H7N9 viruses were selectively expanded and recruited at very early time points after H7N9 challenge, contributing to protective efficacy. The magnitude of the priming virus-generated memory CD8+ T cells was the best predictor of the protective efficacy of the heterosubtypic immunity against subsequent H7N9 challenge in these animals, when compared to the magnitude of the challenge response or the degree of epitope conservation between the priming and challenge strains. These results demonstrate the complexity of cross-reactive CD8+ T cell dynamics and suggest that significant protective immunity can be present even when few epitopes are conserved during heterosubtypic influenza infection.

Vyšlo v časopise: Diverse Heterologous Primary Infections Radically Alter Immunodominance Hierarchies and Clinical Outcomes Following H7N9 Influenza Challenge in Mice. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004642
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004642

Souhrn

Zdroje

1. Gao R, Cao B, Hu Y, Feng Z, Wang D et al. (2013) Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 368: 1888–1897. doi: 10.1056/NEJMoa1304459 23577628

2. Chen E, Chen Y, Fu L, Chen Z, Gong Z et al. (2013) Human infection with avian influenza A(H7N9) virus re-emerges in China in winter 2013. Euro Surveill 18. 24342520

3. Gao HN, Lu HZ, Cao B, Du B, Shang H et al. (2013) Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med 368: 2277–2285. doi: 10.1056/NEJMoa1305584 23697469

4. Yu L, Wang Z, Chen Y, Ding W, Jia H et al. (2013) Clinical, virological, and histopathological manifestations of fatal human infections by avian influenza A(H7N9) virus. Clin Infect Dis 57: 1449–1457. cit541 [pii]; doi: 10.1093/cid/cit541 23943822

5. Li Q, Zhou L, Zhou M, Chen Z, Li F et al. (2014) Epidemiology of human infections with avian influenza A(H7N9) virus in China. N Engl J Med 370: 520–532. doi: 10.1056/NEJMoa1304617 23614499

6. Yamayoshi S, Yamada S, Fukuyama S, Murakami S, Zhao D et al. (2014) Virulence-Affecting Amino Acid Changes in the PA Protein of H7N9 Influenza A Viruses. J Virol 88: 3127–3134. JVI.03155-13 [pii]; doi: 10.1128/JVI.03155-13 24371069

7. Watanabe T, Kiso M, Fukuyama S, Nakajima N, Imai M et al. (2013) Characterization of H7N9 influenza A viruses isolated from humans. Nature 501: 551–555. nature12392 [pii]; doi: 10.1038/nature12392 23842494

8. Xiong X, Martin SR, Haire LF, Wharton SA, Daniels RS et al. (2013) Receptor binding by an H7N9 influenza virus from humans. Nature 499: 496–499. nature12372 [pii]; doi: 10.1038/nature12372 23787694

9. Richard M, Schrauwen EJ, de GM, Bestebroer TM, Spronken MI et al. (2013) Limited airborne transmission of H7N9 influenza A virus between ferrets. Nature 501: 560–563. nature12476 [pii]; doi: 10.1038/nature12476 23925116

10. McMichael AJ, Gotch FM, Noble GR, Beare PA (1983) Cytotoxic T-cell immunity to influenza. N Engl J Med 309: 13–17. doi: 10.1056/NEJM198307073090103 6602294

11. Epstein SL (2006) Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: an experiment of nature. J Infect Dis 193: 49–53. JID35117 [pii]; doi: 10.1086/498980 16323131

12. Hillaire ML, Vogelzang-van Trierum SE, Kreijtz JH, de MG, Fouchier RA et al. (2013) Human T-cells directed to seasonal influenza A virus cross-react with 2009 pandemic influenza A (H1N1) and swine-origin triple-reassortant H3N2 influenza viruses. J Gen Virol 94: 583–592. vir.0.048652-0 [pii]; doi: 10.1099/vir.0.048652-0 23152369

13. Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W et al. (2013) Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med 19: 1305–1312. nm.3350 [pii]; doi: 10.1038/nm.3350 24056771

14. CDC (2014) Seasonal Influenza Q&A.

15. Van Kerkhove MD, Hirve S, Koukounari A, Mounts AW (2013) Estimating age-specific cumulative incidence for the 2009 influenza pandemic: a meta-analysis of A(H1N1)pdm09 serological studies from 19 countries. Influenza Other Respir Viruses 7: 872–886. doi: 10.1111/irv.12074 23331969

16. Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W et al. (2013) Incidence of influenza A(H1N1)pdm09 infection, United Kingdom, 2009-2011. Emerg Infect Dis 19: 1866–1869. doi: 10.3201/eid1911.130295 24188414

17. van de Sandt CE, Kreijtz JH, de MG, Geelhoed-Mieras MM, Hillaire ML et al. (2014) Human cytotoxic T lymphocytes directed to seasonal influenza A viruses cross-react with the newly emerging H7N9 virus. J Virol 88: 1684–1693. JVI.02843-13 [pii]; doi: 10.1128/JVI.02843-13 24257602

18. Tannock GA, Paul JA, Barry RD (1984) Relative immunogenicity of the cold-adapted influenza virus A/Ann Arbor/6/60 (A/AA/6/60-ca), recombinants of A/AA/6/60-ca, and parental strains with similar surface antigens. Infect Immun 43: 457–462. 6693167

19. Mak NK, Zhang YH, Ada GL, Tannock GA (1982) Humoral and cellular responses of mice to infection with a cold-adapted influenza A virus variant. Infect Immun 38: 218–225. 6982860

20. Wang M, Fu CX, Zheng BJ (2009) Antibodies against H5 and H9 avian influenza among poultry workers in China. N Engl J Med 360: 2583–2584. 360/24/2583 [pii]; doi: 10.1056/NEJMc0900358 19516044

21. Liu Y, Lu EJ, Wang YL, Di B, Li TG et al. (2009) [Avian influenza virus infection in people occupied in poultry fields in Guangzhou city]. Zhonghua Liu Xing Bing Xue Za Zhi 30: 1111–1113. 20193575

22. Uyeki TM, Nguyen DC, Rowe T, Lu X, Hu-Primmer J et al. (2012) Seroprevalence of antibodies to avian influenza A (H5) and A (H9) viruses among market poultry workers, Hanoi, Vietnam, 2001. PLoS One 7: e43948. PONE-D-12-15726 [pii]. doi: 10.1371/journal.pone.0043948 22928049

23. Shaw M, Cooper L, Xu X, Thompson W, Krauss S et al. (2002) Molecular changes associated with the transmission of avian influenza a H5N1 and H9N2 viruses to humans. J Med Virol 66: 107–114. [pii]. doi: 10.1002/jmv.2118 11748666

24. Xu KM, Li KS, Smith GJ, Li JW, Tai H et al. (2007) Evolution and molecular epidemiology of H9N2 influenza A viruses from quail in southern China, 2000 to 2005. J Virol 81: 2635–2645. JVI.02316-06 [pii]; doi: 10.1128/JVI.02316-06 17192315

25. Chen Y, Liang W, Yang S, Wu N, Gao H et al. (2013) Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Lancet 381: 1916–1925. S0140-6736(13)60903-4 [pii]; doi: 10.1016/S0140-6736(13)60903-4 23623390

26. Yen HL, Webster RG (2009) Pandemic influenza as a current threat. Curr Top Microbiol Immunol 333: 3–24. doi: 10.1007/978-3-540-92165-3_1 19768398

27. Gras S, Kedzierski L, Valkenburg SA, Laurie K, Liu YC et al. (2010) Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses. Proc Natl Acad Sci U S A 107: 12599–12604. 1007270107 [pii]; doi: 10.1073/pnas.1007270107 20616031

28. Bodewes R, Kreijtz JH, van AG, Hillaire ML, Vogelzang-van Trierum SE et al. (2013) Infection of the upper respiratory tract with seasonal influenza A(H3N2) virus induces protective immunity in ferrets against infection with A(H1N1)pdm09 virus after intranasal, but not intratracheal, inoculation. J Virol 87: 4293–4301. JVI.02536-12 [pii]; doi: 10.1128/JVI.02536-12 23365444

29. Weinfurter JT, Brunner K, Capuano SV III, Li C, Broman KW et al. (2011) Cross-reactive T cells are involved in rapid clearance of 2009 pandemic H1N1 influenza virus in nonhuman primates. PLoS Pathog 7: e1002381. PPATHOGENS-D-11-00455 [pii]. doi: 10.1371/journal.ppat.1002381 22102819

30. Hillaire ML, Osterhaus AD, Rimmelzwaan GF (2011) Induction of virus-specific cytotoxic T lymphocytes as a basis for the development of broadly protective influenza vaccines. J Biomed Biotechnol 2011: 939860. doi: 10.1155/2011/939860 22007149

31. O'Neill E, Krauss SL, Riberdy JM, Webster RG, Woodland DL (2000) Heterologous protection against lethal A/HongKong/156/97 (H5N1) influenza virus infection in C57BL/6 mice. J Gen Virol 81: 2689–2696. 11038381

32. Kreijtz JH, Bodewes R, van den Brand JM, de MG, Baas C et al. (2009) Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus. Vaccine 27: 4983–4989. S0264-410X(09)00817-2 [pii]; doi: 10.1016/j.vaccine.2009.05.079 19538996

33. Grebe KM, Yewdell JW, Bennink JR (2008) Heterosubtypic immunity to influenza A virus: where do we stand? Microbes Infect 10: 1024–1029. S1286-4579(08)00177-9 [pii]; doi: 10.1016/j.micinf.2008.07.002 18662798

34. Lee BO, Rangel-Moreno J, Moyron-Quiroz JE, Hartson L, Makris M et al. (2005) CD4 T cell-independent antibody response promotes resolution of primary influenza infection and helps to prevent reinfection. J Immunol 175: 5827–5838. 175/9/5827 [pii]. 16237075

35. Carragher DM, Kaminski DA, Moquin A, Hartson L, Randall TD (2008) A novel role for non-neutralizing antibodies against nucleoprotein in facilitating resistance to influenza virus. J Immunol 181: 4168–4176. 181/6/4168 [pii]. 18768874

36. Laidlaw BJ, Decman V, Ali MA, Abt MC, Wolf AI et al. (2013) Cooperativity between CD8+ T cells, non-neutralizing antibodies, and alveolar macrophages is important for heterosubtypic influenza virus immunity. PLoS Pathog 9: e1003207. PPATHOGENS-D-11-01388 [pii]. doi: 10.1371/journal.ppat.1003207 23516357

37. Bender BS, Croghan T, Zhang L, Small PA Jr., (1992) Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J Exp Med 175: 1143–1145. 1552285

38. Doherty PC, Turner SJ, Webby RG, Thomas PG (2006) Influenza and the challenge for immunology. Nat Immunol 7: 449–455. ni1343 [pii]; doi: 10.1038/ni1343 16622432

39. Yewdell JW, Bennink JR (1999) Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses. Annu Rev Immunol 17: 51–88. doi: 10.1146/annurev.immunol.17.1.51 10358753

40. Akram A, Inman RD (2012) Immunodominance: a pivotal principle in host response to viral infections. Clin Immunol 143: 99–115. S1521-6616(12)00037-X [pii]; doi: 10.1016/j.clim.2012.01.015 22391152

41. Quinones-Parra S, Grant E, Loh L, Nguyen TH, Campbell KA et al. (2014) Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities. Proc Natl Acad Sci U S A 111: 1049–1054. 1322229111 [pii]; doi: 10.1073/pnas.1322229111 24395804

42. Belz GT, Xie W, Altman JD, Doherty PC (2000) A previously unrecognized H-2D(b)-restricted peptide prominent in the primary influenza A virus-specific CD8(+) T-cell response is much less apparent following secondary challenge. J Virol 74: 3486–3493. 10729122

43. Kedzierska K, La Gruta NL, Turner SJ, Doherty PC (2006) Establishment and recall of CD8+ T-cell memory in a model of localized transient infection. Immunol Rev 211: 133–145. IMR386 [pii]; doi: 10.1111/j.0105-2896.2006.00386.x 16824123

44. Chen W, Pang K, Masterman KA, Kennedy G, Basta S et al. (2004) Reversal in the immunodominance hierarchy in secondary CD8+ T cell responses to influenza A virus: roles for cross-presentation and lysis-independent immunodomination. J Immunol 173: 5021–5027. 173/8/5021 [pii]. 15470045

45. Thomas PG, Brown SA, Keating R, Yue W, Morris MY et al. (2007) Hidden epitopes emerge in secondary influenza virus-specific CD8+ T cell responses. J Immunol 178: 3091–3098. 178/5/3091 [pii]. 17312156

46. The SJCEIRS H9 Working Group. (2013) Assessing the fitness of distinct clades of influenza A (H9N2) viruses. Emerging Microbes and Infections 2: e75. doi: 10.1038/emi.2013.75.

47. Hou S, Hyland L, Ryan KW, Portner A, Doherty PC (1994) Virus-specific CD8+ T-cell memory determined by clonal burst size. Nature 369: 652–654. doi: 10.1038/369652a0 7516039

48. Slutter B, Harty JT (2014) Instructing the instructor: tissue-resident T cells activate innate immunity. Cell Host Microbe 16: 421–423. S1931-3128(14)00344-8 [pii]; doi: 10.1016/j.chom.2014.09.011 25299324

49. Turner SJ, La Gruta NL, Stambas J, Diaz G, Doherty PC (2004) Differential tumor necrosis factor receptor 2-mediated editing of virus-specific CD8+ effector T cells. Proc Natl Acad Sci U S A 101: 3545–3550. 0307347101 [pii]. doi: 10.1073/pnas.0307347101 14993609

50. Belz GT, Xie W, Doherty PC (2001) Diversity of epitope and cytokine profiles for primary and secondary influenza a virus-specific CD8+ T cell responses. J Immunol 166: 4627–4633. 11254721

51. La Gruta NL, Turner SJ, Doherty PC (2004) Hierarchies in cytokine expression profiles for acute and resolving influenza virus-specific CD8+ T cell responses: correlation of cytokine profile and TCR avidity. J Immunol 172: 5553–5560. 15100298

52. Crowe SR, Turner SJ, Miller SC, Roberts AD, Rappolo RA et al. (2003) Differential antigen presentation regulates the changing patterns of CD8+ T cell immunodominance in primary and secondary influenza virus infections. J Exp Med 198: 399–410. jem.20022151 [pii]. doi: 10.1084/jem.20022151 12885871

53. La Gruta NL, Kedzierska K, Pang K, Webby R, Davenport M et al. (2006) A virus-specific CD8+ T cell immunodominance hierarchy determined by antigen dose and precursor frequencies. Proc Natl Acad Sci U S A 103: 994–999. 0510429103 [pii]; doi: 10.1073/pnas.0510429103 16418289

54. Bednarek MA, Sauma SY, Gammon MC, Porter G, Tamhankar S et al. (1991) The minimum peptide epitope from the influenza virus matrix protein. Extra and intracellular loading of HLA-A2. J Immunol 147: 4047–4053. 1721637

55. Boon AC, de MG, Graus YM, Fouchier RA, Sintnicolaas K et al. (2002) The magnitude and specificity of influenza A virus-specific cytotoxic T-lymphocyte responses in humans is related to HLA-A and -B phenotype. J Virol 76: 582–590. 11752149

56. Lehner PJ, Wang EC, Moss PA, Williams S, Platt K et al. (1995) Human HLA-A0201-restricted cytotoxic T lymphocyte recognition of influenza A is dominated by T cells bearing the V beta 17 gene segment. J Exp Med 181: 79–91. 7807026

57. Wu C, Zanker D, Valkenburg S, Tan B, Kedzierska K et al. (2011) Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals. Proc Natl Acad Sci U S A 108: 9178–9183. 1105624108 [pii]; doi: 10.1073/pnas.1105624108 21562214

58. Cukalac T, Valkenburg SA, La Gruta NL, Turner SJ, Doherty PC et al. (2010) Multiplexed combinatorial tetramer staining in a mouse model of virus infection. J Immunol Methods 360: 157–161. S0022-1759(10)00168-7 [pii]; doi: 10.1016/j.jim.2010.06.003 20558170

59. Newell EW, Klein LO, Yu W, Davis MM (2009) Simultaneous detection of many T-cell specificities using combinatorial tetramer staining. Nat Methods 6: 497–499. nmeth.1344 [pii]; doi: 10.1038/nmeth.1344 19543286

60. Yang S, Chen Y, Cui D, Yao H, Lou J et al. (2014) Avian-origin influenza A(H7N9) infection in influenza A(H7N9)-affected areas of China: a serological study. J Infect Dis 209: 265–269. jit430 [pii]; doi: 10.1093/infdis/jit430 23935201

61. Wang X, Fang S, Lu X, Xu C, Cowling BJ et al. (2014) Seroprevalence to avian influenza A(H7N9) virus among poultry workers and the general population in southern China: a longitudinal study. Clin Infect Dis. ciu399 [pii]; doi: 10.1093/cid/ciu399 25552551

62. Slutter B, Pewe LL, Lauer P, Harty JT (2013) Cutting edge: rapid boosting of cross-reactive memory CD8 T cells broadens the protective capacity of the Flumist vaccine. J Immunol 190: 3854–3858. jimmunol.1202790 [pii]; doi: 10.4049/jimmunol.1202790 23467935

63. Wiedmeier SE, Araneo BA, Huang K, Daynes RA (1991) Thymic modulation of IL-2 and IL-4 synthesis by peripheral T cells. Cell Immunol 135: 501–518. 1828013

64. Canonica GW, Ciprandi G, Caria M, Dirienzo W, Shums A et al. (1985) Defect of autologous mixed lymphocyte reaction and interleukin-2 in aged individuals. Mech Ageing Dev 32: 205–212. 2935684

65. Boon AC, Fringuelli E, Graus YM, Fouchier RA, Sintnicolaas K et al. (2002) Influenza A virus specific T cell immunity in humans during aging. Virology 299: 100–108. S0042682202914911 [pii]. 12167345

66. Kohlmeier JE, Connor LM, Roberts AD, Cookenham T, Martin K et al. (2010) Nonmalignant clonal expansions of memory CD8+ T cells that arise with age vary in their capacity to mount recall responses to infection. J Immunol 185: 3456–3462. jimmunol.1001745 [pii]; doi: 10.4049/jimmunol.1001745 20720204

67. Effros RB (1996) Insights on immunological aging derived from the T lymphocyte cellular senescence model. Exp Gerontol 31: 21–27. 0531-5565(95)00017-8 [pii]. 8706791

68. Toapanta FR, Ross TM (2009) Impaired immune responses in the lungs of aged mice following influenza infection. Respir Res 10: 112. 1465-9921-10-112 [pii]; doi: 10.1186/1465-9921-10-112 19922665

69. Bender BS, Taylor SF, Zander DS, Cottey R (1995) Pulmonary immune response of young and aged mice after influenza challenge. J Lab Clin Med 126: 169–177. 7636390

70. Bender BS, Johnson MP, Small PA (1991) Influenza in senescent mice: impaired cytotoxic T-lymphocyte activity is correlated with prolonged infection. Immunology 72: 514–519. 2037313

71. Valkenburg SA, Venturi V, Dang TH, Bird NL, Doherty PC et al. (2012) Early priming minimizes the age-related immune compromise of CD8(+) T cell diversity and function. PLoS Pathog 8: e1002544. PPATHOGENS-D-11-01746 [pii]. doi: 10.1371/journal.ppat.1002544 22383879