1932

Abstract

The 1918 Spanish influenza pandemic was one of the deadliest infectious disease events in recorded history, resulting in approximately 50–100 million deaths worldwide. The origins of the 1918 virus and the molecular basis for its exceptional virulence remained a mystery for much of the 20th century because the pandemic predated virologic techniques to isolate, passage, and store influenza viruses. In the late 1990s, overlapping fragments of influenza viral RNA preserved in the tissues of several 1918 victims were amplified and sequenced. The use of influenza reverse genetics then permitted scientists to reconstruct the 1918 virus entirely from cloned complementary DNA, leading to new insights into the origin of the virus and its pathogenicity. Here, we discuss some of the advances made by resurrection of the 1918 virus, including the rise of innovative molecular research, which is a topic in the dual use debate.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-virology-111821-104408
2023-09-29
2024-05-08
Loading full text...

Full text loading...

/deliver/fulltext/virology/10/1/annurev-virology-111821-104408.html?itemId=/content/journals/10.1146/annurev-virology-111821-104408&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Johnson NP, Mueller J. 2002. Updating the accounts: global mortality of the 1918–1920 “Spanish” influenza pandemic. Bull. Hist. Med. 76:105–15
    [Google Scholar]
  2. 2.
    Murray CJ, Lopez AD, Chin B, Feehan D, Hill KH. 2006. Estimation of potential global pandemic influenza mortality on the basis of vital registry data from the 1918–20 pandemic: a quantitative analysis. Lancet 368:2211–18
    [Google Scholar]
  3. 3.
    Taubenberger JK, Morens DM. 2006. 1918 influenza: the mother of all pandemics. Emerg. Infect. Dis. 12:15–22
    [Google Scholar]
  4. 4.
    Viboud C, Eisenstein J, Reid AH, Janczewski TA, Morens DM, Taubenberger JK. 2013. Age- and sex-specific mortality associated with the 1918–1919 influenza pandemic in Kentucky. J. Infect. Dis. 207:721–29
    [Google Scholar]
  5. 5.
    Shope RE. 1931. The etiology of swine influenza. Science 73:214–15
    [Google Scholar]
  6. 6.
    Reid AH, Fanning TG, Hultin JV, Taubenberger JK. 1999. Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene. PNAS 96:1651–56
    [Google Scholar]
  7. 7.
    Taubenberger JK, Reid AH, Krafft AE, Bijwaard KE, Fanning TG. 1997. Initial genetic characterization of the 1918 “Spanish” influenza virus. Science 275:1793–96
    [Google Scholar]
  8. 8.
    Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG 2005. Characterization of the 1918 influenza virus polymerase genes. Nature 437:889–93
    [Google Scholar]
  9. 9.
    Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solorzano A et al. 2005. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 310:77–80
    [Google Scholar]
  10. 10.
    CDC 2022. Disease burden of flu. Centers for Disease Control and Prevention https://www.cdc.gov/flu/about/burden/index.html
    [Google Scholar]
  11. 11.
    Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R et al. 2018. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet 391:1285–300
    [Google Scholar]
  12. 12.
    Kawaoka Y, Krauss S, Webster RG. 1989. Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J. Virol. 63:4603–8
    [Google Scholar]
  13. 13.
    Scholtissek C, Rohde W, Von Hoyningen V, Rott R. 1978. On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology 87:13–20
    [Google Scholar]
  14. 14.
    Cox NJ, Subbarao K. 2000. Global epidemiology of influenza: past and present. Annu. Rev. Med. 51:407–21
    [Google Scholar]
  15. 15.
    WHO (World Health Organ.) 2017. Pandemic Influenza Risk Management Geneva: World Health Organ.
  16. 16.
    Int. Work. Group Financ. Prep 2017. From panic and neglect to investing in health security: financing pandemic preparedness at a national level Rep. World Bank Washington, DC: https://documents1.worldbank.org/curated/en/979591495652724770/pdf/115271-REVISED-FINAL-IWG-Report-3-5-18.pdf
  17. 17.
    Paules C, Subbarao K. 2017. Influenza. Lancet 390:697–708
    [Google Scholar]
  18. 18.
    Kingsford C, Nagarajan N, Salzberg SL. 2009. 2009 swine-origin influenza A (H1N1) resembles previous influenza isolates. PLOS ONE 4:e6402
    [Google Scholar]
  19. 19.
    Rogers GN, Paulson JC. 1983. Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology 127:361–73
    [Google Scholar]
  20. 20.
    Bosch FX, Garten W, Klenk HD, Rott R. 1981. Proteolytic cleavage of influenza virus hemagglutinins: primary structure of the connecting peptide between HA1 and HA2 determines proteolytic cleavability and pathogenicity of avian influenza viruses. Virology 113:725–35
    [Google Scholar]
  21. 21.
    Goto H, Kawaoka Y. 1998. A novel mechanism for the acquisition of virulence by a human influenza A virus. PNAS 95:10224–28
    [Google Scholar]
  22. 22.
    Goto H, Wells K, Takada A, Kawaoka Y. 2001. Plasminogen-binding activity of neuraminidase determines the pathogenicity of influenza A virus. J. Virol. 75:9297–301
    [Google Scholar]
  23. 23.
    Li S, Schulman J, Itamura S, Palese P. 1993. Glycosylation of neuraminidase determines the neurovirulence of influenza A/WSN/33 virus. J. Virol. 67:6667–73
    [Google Scholar]
  24. 24.
    Reid AH, Fanning TG, Janczewski TA, Taubenberger JK. 2000. Characterization of the 1918 “Spanish” influenza virus neuraminidase gene. PNAS 97:6785–90
    [Google Scholar]
  25. 25.
    Subbarao EK, London W, Murphy BR. 1993. A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J. Virol. 67:1761–64
    [Google Scholar]
  26. 26.
    Basler CF, Reid AH, Dybing JK, Janczewski TA, Fanning TG et al. 2001. Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes. PNAS 98:2746–51
    [Google Scholar]
  27. 27.
    Schafer JR, Kawaoka Y, Bean WJ, Suss J, Senne D, Webster RG. 1993. Origin of the pandemic 1957 H2 influenza A virus and the persistence of its possible progenitors in the avian reservoir. Virology 194:781–88
    [Google Scholar]
  28. 28.
    Kobasa D, Jones SM, Shinya K, Kash JC, Copps J et al. 2007. Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature 445:319–23
    [Google Scholar]
  29. 29.
    Memoli MJ, Tumpey TM, Jagger BW, Dugan VG, Sheng ZM et al. 2009. An early ‘classical’ swine H1N1 influenza virus shows similar pathogenicity to the 1918 pandemic virus in ferrets and mice. Virology 393:338–45
    [Google Scholar]
  30. 30.
    Hatta M, Gao P, Halfmann P, Kawaoka Y. 2001. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293:1840–42
    [Google Scholar]
  31. 31.
    Pappas C, Aguilar PV, Basler CF, Solorzano A, Zeng H et al. 2008. Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus. PNAS 105:3064–69
    [Google Scholar]
  32. 32.
    Conenello GM, Zamarin D, Perrone LA, Tumpey T, Palese P. 2007. A single mutation in the PB1-F2 of H5N1 (HK/97) and 1918 influenza A viruses contributes to increased virulence. PLOS Pathog. 3:1414–21
    [Google Scholar]
  33. 33.
    McAuley JL, Hornung F, Boyd KL, Smith AM, McKeon R et al. 2007. Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe 2:240–49
    [Google Scholar]
  34. 34.
    Watanabe T, Watanabe S, Shinya K, Kim JH, Hatta M, Kawaoka Y. 2009. Viral RNA polymerase complex promotes optimal growth of 1918 virus in the lower respiratory tract of ferrets. PNAS 106:588–92
    [Google Scholar]
  35. 35.
    de Wit E, Siegers JY, Cronin JM, Weatherman S, van den Brand JM et al. 2018. 1918 H1N1 influenza virus replicates and induces proinflammatory cytokine responses in extrarespiratory tissues of ferrets. J. Infect. Dis. 217:1237–46
    [Google Scholar]
  36. 36.
    Schrauwen EJ, Herfst S, Leijten LM, van Run P, Bestebroer TM et al. 2012. The multibasic cleavage site in H5N1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets. J. Virol. 86:3975–84
    [Google Scholar]
  37. 37.
    van den Brand JM, Stittelaar KJ, van Amerongen G, Reperant L, de Waal L et al. 2012. Comparison of temporal and spatial dynamics of seasonal H3N2, pandemic H1N1 and highly pathogenic avian influenza H5N1 virus infections in ferrets. PLOS ONE 7:e42343
    [Google Scholar]
  38. 38.
    Weingartl HM, Albrecht RA, Lager KM, Babiuk S, Marszal P et al. 2009. Experimental infection of pigs with the human 1918 pandemic influenza virus. J. Virol. 83:4287–96
    [Google Scholar]
  39. 39.
    Tumpey TM, Garcia-Sastre A, Mikulasova A, Taubenberger JK, Swayne DE et al. 2002. Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus. PNAS 99:13849–54
    [Google Scholar]
  40. 40.
    Brundage JF, Shanks GD. 2008. Deaths from bacterial pneumonia during 1918–19 influenza pandemic. Emerg. Infect. Dis. 14:1193–99
    [Google Scholar]
  41. 41.
    Chien YW, Klugman KP, Morens DM. 2009. Bacterial pathogens and death during the 1918 influenza pandemic. N. Engl. J. Med. 361:2582–83
    [Google Scholar]
  42. 42.
    Morens DM, Taubenberger JK, Fauci AS. 2008. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J. Infect. Dis. 198:962–70
    [Google Scholar]
  43. 43.
    Brightman IJ. 1935. Streptococcus infection occurring in ferrets inoculated with human influenza virus. Yale J. Biol. Med. 8:127–35
    [Google Scholar]
  44. 44.
    Short KR, Habets MN, Hermans PW, Diavatopoulos DA. 2012. Interactions between Streptococcus pneumoniae and influenza virus: a mutually beneficial relationship?. Future Microbiol. 7:609–24
    [Google Scholar]
  45. 45.
    Short KR, Reading PC, Brown LE, Pedersen J, Gilbertson B et al. 2013. Influenza-induced inflammation drives pneumococcal otitis media. Infect. Immun. 81:645–52
    [Google Scholar]
  46. 46.
    Wilson HE, Saslaw S, Doan CA, Woolpert OC, Schwab JL. 1947. Reactions of monkeys to experimental mixed influenza and streptococcus infections: an analysis of the relative roles of humoral and cellular immunity, with the description of an intercurrent nephritic syndrome. J. Exp. Med. 85:199–215
    [Google Scholar]
  47. 47.
    Shope RE. 1931. Swine influenza: III. Filtration experiments and etiology. J. Exp. Med. 54:373–85
    [Google Scholar]
  48. 48.
    Diavatopoulos DA, Short KR, Price JT, Wilksch JJ, Brown LE et al. 2010. Influenza A virus facilitates Streptococcus pneumoniae transmission and disease. FASEB J. 24:1789–98
    [Google Scholar]
  49. 49.
    Short KR, Reading PC, Wang N, Diavatopoulos DA, Wijburg OL. 2012. Increased nasopharyngeal bacterial titers and local inflammation facilitate transmission of Streptococcus pneumoniae. mBio 3:e00255–12
    [Google Scholar]
  50. 50.
    Louria DB, Blumenfeld HL, Ellis JT, Kilbourne ED, Rogers DE. 1959. Studies on influenza in the pandemic of 1957–1958. II. Pulmonary complications of influenza. J. Clin. Invest. 38:213–65
    [Google Scholar]
  51. 51.
    Oseasohn R, Adelson L, Kaji M. 1959. Clinicopathologic study of thirty-three fatal cases of Asian influenza. N. Engl. J. Med. 260:509–18
    [Google Scholar]
  52. 52.
    Oswald NC, Shooter RA, Curwen MP. 1958. Pneumonia complicating Asian influenza. Br. Med. J. 2:1305–11
    [Google Scholar]
  53. 53.
    Robertson L, Caley JP, Moore J. 1958. Importance of Staphylococcus aureus in pneumonia in the 1957 epidemic of influenza A. Lancet 2:233–36
    [Google Scholar]
  54. 54.
    Tashiro M, Ciborowski P, Klenk HD, Pulverer G, Rott R. 1987. Role of Staphylococcus protease in the development of influenza pneumonia. Nature 325:536–37
    [Google Scholar]
  55. 55.
    Fainstein V, Musher DM, Cate TR. 1980. Bacterial adherence to pharyngeal cells during viral infection. J. Infect. Dis. 141:172–76
    [Google Scholar]
  56. 56.
    Plotkowski MC, Puchelle E, Beck G, Jacquot J, Hannoun C. 1986. Adherence of type I Streptococcus pneumoniae to tracheal epithelium of mice infected with influenza A/PR8 virus. Am. Rev. Respir. Dis. 134:1040–44
    [Google Scholar]
  57. 57.
    Kash JC, Walters KA, Davis AS, Sandouk A, Schwartzman LM et al. 2011. Lethal synergism of 2009 pandemic H1N1 influenza virus and Streptococcus pneumoniae coinfection is associated with loss of murine lung repair responses. mBio 2:e00172–11
    [Google Scholar]
  58. 58.
    Brundage JF. 2006. Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness. Lancet Infect. Dis. 6:303–12
    [Google Scholar]
  59. 59.
    Peltola VT, McCullers JA. 2004. Respiratory viruses predisposing to bacterial infections: role of neuraminidase. Pediatr. Infect. Dis. J. 23:S87–97
    [Google Scholar]
  60. 60.
    Wu Y, Mao H, Ling MT, Chow KH, Ho PL et al. 2011. Successive influenza virus infection and Streptococcus pneumoniae stimulation alter human dendritic cell function. BMC Infect. Dis. 11:201
    [Google Scholar]
  61. 61.
    Hakansson A, Kidd A, Wadell G, Sabharwal H, Svanborg C. 1994. Adenovirus infection enhances in vitro adherence of Streptococcus pneumoniae. Infect. Immun. 62:2707–14
    [Google Scholar]
  62. 62.
    Ballinger MN, Standiford TJ. 2010. Postinfluenza bacterial pneumonia: host defenses gone awry. J. Interferon Cytokine Res. 30:643–52
    [Google Scholar]
  63. 63.
    Nakamura S, Davis KM, Weiser JN. 2011. Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice. J. Clin. Invest. 121:3657–65
    [Google Scholar]
  64. 64.
    Jain S, Benoit SR, Skarbinski J, Bramley AM, Finelli L. 2012. Influenza-associated pneumonia among hospitalized patients with 2009 pandemic influenza A (H1N1) virus—United States, 2009. Clin. Infect. Dis. 54:1221–29
    [Google Scholar]
  65. 65.
    Memoli MJ, Morens DM, Taubenberger JK. 2008. Pandemic and seasonal influenza: therapeutic challenges. Drug Discov. Today 13:590–95
    [Google Scholar]
  66. 66.
    Millard J, Ugarte-Gil C, Moore DA. 2015. Multidrug resistant tuberculosis. BMJ 350:h882
    [Google Scholar]
  67. 67.
    Zumla A, Raviglione M, Hafner R, von Reyn CF. 2013. Tuberculosis. N. Engl. J. Med. 368:745–55
    [Google Scholar]
  68. 68.
    Ventola CL. 2015. The antibiotic resistance crisis: part 2: management strategies and new agents. Pharm. Ther. 40:344–52
    [Google Scholar]
  69. 69.
    Ventola CL. 2015. The antibiotic resistance crisis: part 1: causes and threats. Pharm. Ther. 40:277–83
    [Google Scholar]
  70. 70.
    Claas EC, Osterhaus AD, van Beek R, De Jong JC, Rimmelzwaan GF et al. 1998. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 351:472–77
    [Google Scholar]
  71. 71.
    Guan Y, Peiris JS, Lipatov AS, Ellis TM, Dyrting KC et al. 2002. Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR. PNAS 99:8950–55
    [Google Scholar]
  72. 72.
    Subbarao K, Klimov A, Katz J, Regnery H, Lim W et al. 1998. Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 279:393–96
    [Google Scholar]
  73. 73.
    Yuen KY, Chan PK, Peiris M, Tsang DN, Que TL et al. 1998. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 351:467–71
    [Google Scholar]
  74. 74.
    Guan Y, Shortridge KF, Krauss S, Webster RG. 1999. Molecular characterization of H9N2 influenza viruses: Were they the donors of the “internal” genes of H5N1 viruses in Hong Kong?. PNAS 96:9363–67
    [Google Scholar]
  75. 75.
    Hoffmann E, Stech J, Leneva I, Krauss S, Scholtissek C et al. 2000. Characterization of the influenza A virus gene pool in avian species in southern China: Was H6N1 a derivative or a precursor of H5N1?. J. Virol. 74:6309–15
    [Google Scholar]
  76. 76.
    Xu X, Subbarao K, Cox NJ, Guo Y. 1999. Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong. Virology 261:15–19
    [Google Scholar]
  77. 77.
    Lin YP, Shaw M, Gregory V, Cameron K, Lim W et al. 2000. Avian-to-human transmission of H9N2 subtype influenza A viruses: relationship between H9N2 and H5N1 human isolates. PNAS 97:9654–58
    [Google Scholar]
  78. 78.
    Shortridge KF. 1999. Poultry and the influenza H5N1 outbreak in Hong Kong, 1997: abridged chronology and virus isolation. Vaccine 17:Suppl. 1S26–29
    [Google Scholar]
  79. 79.
    Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF et al. 2004. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet 363:617–19
    [Google Scholar]
  80. 80.
    Caliendo V, Lewis NS, Pohlmann A, Baillie SR, Banyard AC et al. 2022. Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021. Sci. Rep. 12:11729
    [Google Scholar]
  81. 81.
    Cui P, Shi J, Wang C, Zhang Y, Xing X et al. 2022. Global dissemination of H5N1 influenza viruses bearing the clade 2.3.4.4b HA gene and biologic analysis of the ones detected in China. Emerg. Microbes Infect. 11:1693–704
    [Google Scholar]
  82. 82.
    Pohlmann A, King J, Fusaro A, Zecchin B, Banyard AC et al. 2022. Has epizootic become enzootic? Evidence for a fundamental change in the infection dynamics of highly pathogenic avian influenza in Europe, 2021. mBio 13:e0060922
    [Google Scholar]
  83. 83.
    Alkie TN, Lopes S, Hisanaga T, Xu W, Suderman M et al. 2022. A threat from both sides: multiple introductions of genetically distinct H5 HPAI viruses into Canada via both East Asia-Australasia/Pacific and Atlantic flyways. Virus Evol. 8:veac077
    [Google Scholar]
  84. 84.
    Natl. Wildl. Health Cent 2022. Distribution of highly pathogenic avian influenza H5 and H5N1 in North America, 2021/2022. US Geological Survey https://www.usgs.gov/media/images/distribution-highly-pathogenic-avian-influenza-h5-and-h5n1-north-america-20212022
    [Google Scholar]
  85. 85.
    Cheung CY, Poon LL, Lau AS, Luk W, Lau YL et al. 2002. Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease?. Lancet 360:1831–37
    [Google Scholar]
  86. 86.
    Matsuoka Y, Swayne DE, Thomas C, Rameix-Welti MA, Naffakh N et al. 2009. Neuraminidase stalk length and additional glycosylation of the hemagglutinin influence the virulence of influenza H5N1 viruses for mice. J. Virol. 83:4704–8
    [Google Scholar]
  87. 87.
    Suguitan AL Jr., Matsuoka Y, Lau YF, Santos CP, Vogel L et al. 2012. The multibasic cleavage site of the hemagglutinin of highly pathogenic A/Vietnam/1203/2004 (H5N1) avian influenza virus acts as a virulence factor in a host-specific manner in mammals. J. Virol. 86:2706–14
    [Google Scholar]
  88. 88.
    Ehrhardt C, Wolff T, Pleschka S, Planz O, Beermann W et al. 2007. Influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate antiapoptotic signaling responses. J. Virol. 81:3058–67
    [Google Scholar]
  89. 89.
    Jackson D, Hossain MJ, Hickman D, Perez DR, Lamb RA. 2008. A new influenza virus virulence determinant: the NS1 protein four C-terminal residues modulate pathogenicity. PNAS 105:4381–86
    [Google Scholar]
  90. 90.
    Li Z, Jiang Y, Jiao P, Wang A, Zhao F et al. 2006. The NS1 gene contributes to the virulence of H5N1 avian influenza viruses. J. Virol. 80:11115–23
    [Google Scholar]
  91. 91.
    Karron RA, Talaat K, Luke C, Callahan K, Thumar B et al. 2009. Evaluation of two live attenuated cold-adapted H5N1 influenza virus vaccines in healthy adults. Vaccine 27:4953–60
    [Google Scholar]
  92. 92.
    Li C, Bu Z, Chen H. 2014. Avian influenza vaccines against H5N1 ‘bird flu. .’ Trends Biotechnol. 32:147–56
    [Google Scholar]
  93. 93.
    Shi J, Zeng X, Cui P, Yan C, Chen H. 2023. Alarming situation of emerging H5 and H7 avian influenza and effective control strategies. Emerg. Microbes Infect. 12:2155072
    [Google Scholar]
  94. 94.
    Subbarao K, Chen H, Swayne D, Mingay L, Fodor E et al. 2003. Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics. Virology 305:192–200
    [Google Scholar]
  95. 95.
    Suguitan AL Jr., McAuliffe J, Mills KL, Jin H, Duke G et al. 2006. Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets. PLOS Med. 3:e360
    [Google Scholar]
  96. 96.
    Talaat KR, Luke CJ, Khurana S, Manischewitz J, King LR et al. 2014. A live attenuated influenza A (H5N1) vaccine induces long-term immunity in the absence of a primary antibody response. J. Infect. Dis. 209:1860–69
    [Google Scholar]
  97. 97.
    Webby RJ, Perez DR, Coleman JS, Guan Y, Knight JH et al. 2004. Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines. Lancet 363:1099–103
    [Google Scholar]
  98. 98.
    World Health Organ 2022. Recommended composition of influenza virus vaccines for use in the 2022–2023 Northern Hemisphere influenza season. Wkly. Epidemiol. Record 97:109–32
    [Google Scholar]
  99. 99.
    Herfst S, Schrauwen EJ, Linster M, Chutinimitkul S, de Wit E et al. 2012. Airborne transmission of influenza A/H5N1 virus between ferrets. Science 336:1534–41
    [Google Scholar]
  100. 100.
    Imai M, Watanabe T, Hatta M, Das SC, Ozawa M et al. 2012. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 486:420–28
    [Google Scholar]
  101. 101.
    Dermody TS, Sandri-Goldin RM, Shenk T. 2013. A new determinant of H5N1 influenza virus pathogenesis in mammals. J. Virol. 87:4795–96
    [Google Scholar]
  102. 102.
    Zaraket H, Bridges OA, Russell CJ. 2013. The pH of activation of the hemagglutinin protein regulates H5N1 influenza virus replication and pathogenesis in mice. J. Virol. 87:4826–34
    [Google Scholar]
  103. 103.
    Sutton TC, Finch C, Shao H, Angel M, Chen H et al. 2014. Airborne transmission of highly pathogenic H7N1 influenza virus in ferrets. J. Virol. 88:6623–35
    [Google Scholar]
  104. 104.
    Guan Y, Zheng BJ, He YQ, Liu XL, Zhuang ZX et al. 2003. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 302:276–78
    [Google Scholar]
  105. 105.
    Haagmans BL, Al Dhahiry SH, Reusken CB, Raj VS, Galiano M et al. 2014. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect. Dis. 14:140–45
    [Google Scholar]
  106. 106.
    Lau SK, Woo PC, Li KS, Huang Y, Tsoi HW et al. 2005. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. PNAS 102:14040–45
    [Google Scholar]
  107. 107.
    Li W, Shi Z, Yu M, Ren W, Smith C et al. 2005. Bats are natural reservoirs of SARS-like coronaviruses. Science 310:676–79
    [Google Scholar]
  108. 108.
    Xiong Q, Cao L, Ma C, Tortorici MA, Liu C et al. 2022. Close relatives of MERS-CoV in bats use ACE2 as their functional receptors. Nature 612:748–57
    [Google Scholar]
  109. 109.
    Menachery VD, Yount BL Jr., Debbink K, Agnihothram S, Gralinski LE et al. 2015. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat. Med. 21:1508–13
    [Google Scholar]
  110. 110.
    World Health Organ 2023. WHO coronavirus (COVID-19) dashboard. World Health Organization. https://covid19.who.int/
    [Google Scholar]
  111. 111.
    De Clercq E. 2019. Fifty years in search of selective antiviral drugs. J. Med. Chem. 62:7322–39
    [Google Scholar]
  112. 112.
    Xu S, Ding D, Zhang X, Sun L, Kang D et al. 2022. Newly emerging strategies in antiviral drug discovery: dedicated to Prof. Dr. Erik De Clercq on occasion of his 80th anniversary. Molecules 27:850
    [Google Scholar]
  113. 113.
    Ma Y, Frutos-Beltran E, Kang D, Pannecouque C, De Clercq E et al. 2021. Medicinal chemistry strategies for discovering antivirals effective against drug-resistant viruses. Chem. Soc. Rev. 50:4514–40
    [Google Scholar]
  114. 114.
    Lai AC, Crews CM. 2017. Induced protein degradation: an emerging drug discovery paradigm. Nat. Rev. Drug Discov. 16:101–14
    [Google Scholar]
  115. 115.
    Si L, Shen Q, Li J, Chen L, Shen J et al. 2022. Generation of a live attenuated influenza A vaccine by proteolysis targeting. Nat. Biotechnol. 40:1370–77
    [Google Scholar]
  116. 116.
    Costales MG, Aikawa H, Li Y, Childs-Disney JL, Abegg D et al. 2020. Small-molecule targeted recruitment of a nuclease to cleave an oncogenic RNA in a mouse model of metastatic cancer. PNAS 117:2406–11
    [Google Scholar]
  117. 117.
    Costales MG, Suresh B, Vishnu K, Disney MD. 2019. Targeted degradation of a hypoxia-associated non-coding RNA enhances the selectivity of a small molecule interacting with RNA. Cell Chem. Biol. 26:1180–86.e5
    [Google Scholar]
  118. 118.
    Bauer RA. 2015. Covalent inhibitors in drug discovery: from accidental discoveries to avoided liabilities and designed therapies. Drug Discov. Today 20:1061–73
    [Google Scholar]
  119. 119.
    Nie C, Parshad B, Bhatia S, Cheng C, Stadtmuller M et al. 2020. Topology-matching design of an influenza-neutralizing spiky nanoparticle-based inhibitor with a dual mode of action. Angew. Chem. Weinheim. Bergstr. Ger. 132:15662–66
    [Google Scholar]
  120. 120.
    Chen R, Wang T, Song J, Pu D, He D et al. 2021. Antiviral drug delivery system for enhanced bioactivity, better metabolism and pharmacokinetic characteristics. Int. J. Nanomed. 16:4959–84
    [Google Scholar]
  121. 121.
    Jagger BW, Wise HM, Kash JC, Walters KA, Wills NM et al. 2012. An overlapping protein-coding region in influenza A virus segment 3 modulates the host response. Science 337:199–204
    [Google Scholar]
  122. 122.
    Chen D-Y, Kenney D, Chin CV, Tavares AH, Khan N et al. 2022. Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1 Omicron. bioRxiv 2022.10.13.512134. https://doi.org/10.1101/2022.10.13.512134
    [Crossref]
  123. 123.
    Neumann G, Watanabe T, Ito H, Watanabe S, Goto H et al. 1999. Generation of influenza A viruses entirely from cloned cDNAs. PNAS 96:9345–50
    [Google Scholar]
  124. 124.
    Kanai Y, Komoto S, Kawagishi T, Nouda R, Nagasawa N et al. 2017. Entirely plasmid-based reverse genetics system for rotaviruses. PNAS 114:2349–54
    [Google Scholar]
  125. 125.
    Gan T, Zhou D, Huang Y, Xiao S, Ma Z et al. 2021. Development of a new reverse genetics system for Ebola virus. mSphere 6:e00235–21
    [Google Scholar]
  126. 126.
    Tsuda Y, Hoenen T, Banadyga L, Weisend C, Ricklefs SM et al. 2015. An improved reverse genetics system to overcome cell-type-dependent Ebola virus genome plasticity. J. Infect. Dis. 212:Suppl. 2S129–37
    [Google Scholar]
  127. 127.
    Volchkov VE, Volchkova VA, Muhlberger E, Kolesnikova LV, Weik M et al. 2001. Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP gene and viral cytotoxicity. Science 291:1965–69
    [Google Scholar]
  128. 128.
    Yoneda M, Guillaume V, Ikeda F, Sakuma Y, Sato H et al. 2006. Establishment of a Nipah virus rescue system. PNAS 103:16508–13
    [Google Scholar]
  129. 129.
    Yount B, Curtis KM, Fritz EA, Hensley LE, Jahrling PB et al. 2003. Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus. PNAS 100:12995–3000
    [Google Scholar]
  130. 130.
    Almazan F, DeDiego ML, Sola I, Zuniga S, Nieto-Torres JL et al. 2013. Engineering a replication-competent, propagation-defective Middle East respiratory syndrome coronavirus as a vaccine candidate. mBio 4:e00650–13
    [Google Scholar]
  131. 131.
    Amarilla AA, Sng JDJ, Parry R, Deerain JM, Potter JR et al. 2021. A versatile reverse genetics platform for SARS-CoV-2 and other positive-strand RNA viruses. Nat. Commun. 12:3431
    [Google Scholar]
  132. 132.
    Ye C, Chiem K, Park JG, Oladunni F, Platt RN 2nd et al. 2020. Rescue of SARS-CoV-2 from a single bacterial artificial chromosome. mBio 11:e02168–20
    [Google Scholar]
  133. 133.
    Wimmer E, Mueller S, Tumpey TM, Taubenberger JK. 2009. Synthetic viruses: a new opportunity to understand and prevent viral disease. Nat. Biotechnol. 27:1163–72
    [Google Scholar]
  134. 134.
    Jackson RJ, Ramsay AJ, Christensen CD, Beaton S, Hall DF, Ramshaw IA. 2001. Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox. J. Virol. 75:1205–10
    [Google Scholar]
  135. 135.
    Cello J, Paul AV, Wimmer E. 2002. Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template. Science 297:1016–18
    [Google Scholar]
  136. 136.
    Almazan F, Gonzalez JM, Penzes Z, Izeta A, Calvo E et al. 2000. Engineering the largest RNA virus genome as an infectious bacterial artificial chromosome. PNAS 97:5516–21
    [Google Scholar]
  137. 137.
    Thiel V, Herold J, Schelle B, Siddell SG. 2001. Infectious RNA transcribed in vitro from a cDNA copy of the human coronavirus genome cloned in vaccinia virus. J. Gen. Virol. 82:1273–81
    [Google Scholar]
  138. 138.
    Thi Nhu Thao T, Labroussaa F, Ebert N, V'Kovski P, Stalder H et al. 2020. Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform. Nature 582:561–65
    [Google Scholar]
  139. 139.
    Torii S, Ono C, Suzuki R, Morioka Y, Anzai I et al. 2021. Establishment of a reverse genetics system for SARS-CoV-2 using circular polymerase extension reaction. Cell Rep. 35:109014
    [Google Scholar]
  140. 140.
    Xie X, Lokugamage KG, Zhang X, Vu MN, Muruato AE et al. 2021. Engineering SARS-CoV-2 using a reverse genetic system. Nat. Protoc. 16:1761–84
    [Google Scholar]
  141. 141.
    Edmonds J, van Grinsven E, Prow N, Bosco-Lauth A, Brault AC et al. 2013. A novel bacterium-free method for generation of flavivirus infectious DNA by circular polymerase extension reaction allows accurate recapitulation of viral heterogeneity. J. Virol. 87:2367–72
    [Google Scholar]
  142. 142.
    Berger Rentsch M, Zimmer G. 2011. A vesicular stomatitis virus replicon-based bioassay for the rapid and sensitive determination of multi-species type I interferon. PLOS ONE 6:e25858
    [Google Scholar]
  143. 143.
    de Vries E, Tscherne DM, Wienholts MJ, Cobos-Jimenez V, Scholte F et al. 2011. Dissection of the influenza A virus endocytic routes reveals macropinocytosis as an alternative entry pathway. PLOS Pathog. 7:e1001329
    [Google Scholar]
  144. 144.
    Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T et al. 2020. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181:271–80.e8
    [Google Scholar]
  145. 145.
    Miyauchi K, Kim Y, Latinovic O, Morozov V, Melikyan GB. 2009. HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes. Cell 137:433–44
    [Google Scholar]
  146. 146.
    Nanbo A, Imai M, Watanabe S, Noda T, Takahashi K et al. 2010. Ebolavirus is internalized into host cells via macropinocytosis in a viral glycoprotein-dependent manner. PLOS Pathog. 6:e1001121
    [Google Scholar]
  147. 147.
    Schelhaas M, Shah B, Holzer M, Blattmann P, Kuhling L et al. 2012. Entry of human papillomavirus type 16 by actin-dependent, clathrin- and lipid raft-independent endocytosis. PLOS Pathog. 8:e1002657
    [Google Scholar]
  148. 148.
    Crawford KHD, Eguia R, Dingens AS, Loes AN, Malone KD et al. 2020. Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays. Viruses 12:513
    [Google Scholar]
  149. 149.
    Plante JA, Liu Y, Liu J, Xia H, Johnson BA et al. 2021. Spike mutation D614G alters SARS-CoV-2 fitness. Nature 592:116–21
    [Google Scholar]
  150. 150.
    Syed AM, Taha TY, Tabata T, Chen IP, Ciling A et al. 2021. Rapid assessment of SARS-CoV-2–evolved variants using virus-like particles. Science 374:1626–32
    [Google Scholar]
  151. 151.
    Zhang X, Liu Y, Liu J, Bailey AL, Plante KS et al. 2021. A trans-complementation system for SARS-CoV-2 recapitulates authentic viral replication without virulence. Cell 184:2229–38.e13
    [Google Scholar]
  152. 152.
    Morens DM, Taubenberger JK, Fauci AS. 2013. Pandemic influenza viruses—hoping for the road not taken. N. Engl. J. Med. 368:2345–48
    [Google Scholar]
  153. 153.
    Wain-Hobson S. 2013. Pandemic influenza viruses: time to recognize our inability to predict the unpredictable and stop dangerous gain-of-function experiments. EMBO Mol. Med. 5:1637–41
    [Google Scholar]
  154. 154.
    Gong LI, Suchard MA, Bloom JD. 2013. Stability-mediated epistasis constrains the evolution of an influenza protein. eLife 2:e00631
    [Google Scholar]
  155. 155.
    Kryazhimskiy S, Dushoff J, Bazykin GA, Plotkin JB. 2011. Prevalence of epistasis in the evolution of influenza A surface proteins. PLOS Genet. 7:e1001301
    [Google Scholar]
  156. 156.
    Shelton H, Ayora-Talavera G, Ren J, Loureiro S, Pickles RJ et al. 2011. Receptor binding profiles of avian influenza virus hemagglutinin subtypes on human cells as a predictor of pandemic potential. J. Virol. 85:1875–80
    [Google Scholar]
  157. 157.
    Shelton H, Roberts KL, Molesti E, Temperton N, Barclay WS. 2013. Mutations in haemagglutinin that affect receptor binding and pH stability increase replication of a PR8 influenza virus with H5 HA in the upper respiratory tract of ferrets and may contribute to transmissibility. J. Gen. Virol. 94:1220–29
    [Google Scholar]
  158. 158.
    Tharakaraman K, Raman R, Viswanathan K, Stebbins NW, Jayaraman A et al. 2013. Structural determinants for naturally evolving H5N1 hemagglutinin to switch its receptor specificity. Cell 153:1475–85
    [Google Scholar]
  159. 159.
    Cox NJ, Trock SC, Burke SA. 2014. Pandemic preparedness and the Influenza Risk Assessment Tool (IRAT). Curr. Top. Microbiol. Immunol. 385:119–36
    [Google Scholar]
  160. 160.
    Maines TR, Chen LM, Van Hoeven N, Tumpey TM, Blixt O et al. 2011. Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses. Virology 413:139–47
    [Google Scholar]
  161. 161.
    Richard M, Schrauwen EJ, de Graaf M, Bestebroer TM, Spronken MI et al. 2013. Limited airborne transmission of H7N9 influenza A virus between ferrets. Nature 501:560–63
    [Google Scholar]
  162. 162.
    Zhang Y, Zhang Q, Kong H, Jiang Y, Gao Y et al. 2013. H5N1 hybrid viruses bearing 2009/H1N1 virus genes transmit in guinea pigs by respiratory droplet. Science 340:1459–63
    [Google Scholar]
  163. 163.
    Getz LJ, Dellaire G. 2018. Angels and devils: dilemmas in dual-use biotechnology. Trends Biotechnol 36:1202–5
    [Google Scholar]
  164. 164.
    Natl. Health Med. Res. Counc 2022. Gain-of-function research review: report Rep. NHMRC Canberra: Aust. https://www.nhmrc.gov.au/about-us/publications/gain-function-research-review-report
  165. 165.
    Webby RJ, Webster RG. 2003. Are we ready for pandemic influenza?. Science 302:1519–22
    [Google Scholar]
  166. 166.
    World Health Organ 2022. Cumulative number of confirmed human cases for avian influenza A(H5N1) reported to WHO, 2003–2022, 5 October 2022. World Health Organization. https://www.who.int/publications/m/item/cumulative-number-of-confirmed-human-cases-for-avian-influenza-a(h5n1)-reported-to-who-2003-2022-5-oct-2022
    [Google Scholar]
  167. 167.
    Casadevall A, Fang FC. 2009. Important science—It's all about the SPIN. Infect. Immun. 77:4177–80
    [Google Scholar]
  168. 168.
    Patrono LV, Vrancken B, Budt M, Düx A, Lequime S et al. 2022. Archival influenza virus genomes from Europe reveal genomic variability during the 1918 pandemic. Nat. Commun. 13:2314
    [Google Scholar]
  169. 169.
    Jordan D. 2019. The deadliest flu: the complete story of the discovery and reconstruction of the 1918 pandemic virus. Centers for Disease Control and Prevention. https://www.cdc.gov/flu/pandemic-resources/reconstruction-1918-virus.html
    [Google Scholar]
/content/journals/10.1146/annurev-virology-111821-104408
Loading
/content/journals/10.1146/annurev-virology-111821-104408
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error