1932

Abstract

The concept of influenza A virus (IAV) subpopulations emerged approximately 75 years ago, when Preben von Magnus described “incomplete” virus particles that interfere with the replication of infectious virus. It is now widely accepted that infectious particles constitute only a minor portion of biologically active IAV subpopulations. The IAV quasispecies is an extremely diverse swarm of biologically and genetically heterogeneous particle subpopulations that collectively influence the evolutionary fitness of the virus. This review summarizes the current knowledge of IAV subpopulations, focusing on their biologic and genomic diversity. It also discusses the potential roles IAV subpopulations play in virus pathogenesis and live attenuated influenza vaccine development.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-animal-021419-083756
2020-02-15
2024-12-04
Loading full text...

Full text loading...

/deliver/fulltext/animal/8/1/annurev-animal-021419-083756.html?itemId=/content/journals/10.1146/annurev-animal-021419-083756&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Neumann G, Kawaoka Y. 2019. Can we predict the next influenza pandemics?. J. Infect. Dis. 219:S14–S20
    [Google Scholar]
  2. 2. 
    Erbelding EJ, Post DJ, Stemmy EJ, Roberts PC, Augustine AD et al. 2018. A universal influenza vaccine: the strategic plan for the National Institute of Allergy and Infectious Diseases. J. Infect. Dis. 218:347–54
    [Google Scholar]
  3. 3. 
    Dadonaite B, Vijayakrishnan S, Fodor E, Bhella D, Hutchinson EC 2016. Filamentous influenza viruses. J. Gen. Virol. 97:1755–64
    [Google Scholar]
  4. 4. 
    Chou YY, Vafabakhsh R, Doğanay S, Gao Q, Ha T, Palese P 2012. One influenza virus particle packages eight unique viral RNAs as shown by FISH analysis. PNAS 109:9101–6
    [Google Scholar]
  5. 5. 
    Noda T, Sagara H, Yen A, Takada A, Kida H et al. 2006. Architecture of ribonucleoprotein complexes in influenza A virus particles. Nature 439:490–92
    [Google Scholar]
  6. 6. 
    Bouvier NM, Palese P. 2008. The biology of influenza viruses. Vaccine 26:Suppl. 4D49–53
    [Google Scholar]
  7. 7. 
    Abraham G. 1979. The effect of ultraviolet radiation on the primary transcription of influenza virus messenger RNAs. Virology 97:177–82
    [Google Scholar]
  8. 8. 
    Eisfeld AJ, Neumann G, Kawaoka Y 2015. At the centre: influenza A virus ribonucleoproteins. Nat. Rev. Microbiol. 13:28–41
    [Google Scholar]
  9. 9. 
    Sobel Leonard A, McClain MT, Smith GJ, Wentworth DE, Halpin RA et al. 2016. Deep sequencing of influenza A virus from a human challenge study reveals a selective bottleneck and only limited intrahost genetic diversification. J. Virol. 90:11247–58
    [Google Scholar]
  10. 10. 
    Xiao YL, Ren L, Zhang X, Qi L, Kash JC et al. 2018. Deep sequencing of H7N9 influenza A viruses from 16 infected patients from 2013 to 2015 in Shanghai reveals genetic diversity and antigenic drift. mSphere 3:5e00462-18
    [Google Scholar]
  11. 11. 
    Domingo E, Sheldon J, Perales C 2012. Viral quasispecies evolution. Microbiol. Mol. Biol. Rev. 76:159–216
    [Google Scholar]
  12. 12. 
    Yoon SW, Webby RJ, Webster RG 2014. Evolution and ecology of influenza A viruses. Curr. Top. Microbiol. Immunol. 385:359–75
    [Google Scholar]
  13. 13. 
    Donald HB, Isaacs A. 1954. Counts of influenza virus particles. J. Gen. Microbiol. 10:457–64
    [Google Scholar]
  14. 14. 
    Ngunjiri JM, Sekellick MJ, Marcus PI 2008. Clonogenic assay of type A influenza viruses reveals noninfectious cell-killing (apoptosis-inducing) particles. J. Virol. 82:2673–80
    [Google Scholar]
  15. 15. 
    Marcus PI, Ngunjiri JM, Sekellick MJ 2009. Dynamics of biologically active subpopulations of influenza virus: plaque-forming, noninfectious cell-killing, and defective interfering particles. J. Virol. 83:8122–30
    [Google Scholar]
  16. 16. 
    Levine S, Puck TT, Sagik BP 1953. An absolute method for assay of virus hemagglutinins. J. Exp. Med. 98:521–31
    [Google Scholar]
  17. 17. 
    Diefenbacher M, Sun J, Brooke CB 2018. The parts are greater than the whole: the role of semi-infectious particles in influenza A virus biology. Curr. Opin. Virol. 33:42–46
    [Google Scholar]
  18. 18. 
    Brooke CB. 2017. Population diversity and collective interactions during influenza virus infection. J. Virol. 91:e01164-17
    [Google Scholar]
  19. 19. 
    Brooke CB, Ince WL, Wrammert J, Ahmed R, Wilson PC et al. 2013. Most influenza A virions fail to express at least one essential viral protein. J. Virol. 87:3155–62
    [Google Scholar]
  20. 20. 
    Bartolini B, Chillemi G, Abbate I, Bruselles A, Rozera G et al. 2011. Assembly and characterization of pandemic influenza A H1N1 genome in nasopharyngeal swabs using high-throughput pyrosequencing. New Microbiol 34:391–97
    [Google Scholar]
  21. 21. 
    Flaherty P, Natsoulis G, Muralidharan O, Winters M, Buenrostro J et al. 2012. Ultrasensitive detection of rare mutations using next-generation targeted resequencing. Nucleic Acids Res 40:e2
    [Google Scholar]
  22. 22. 
    Iqbal M, Xiao H, Baillie G, Warry A, Essen SC et al. 2009. Within-host variation of avian influenza viruses. Philos. Trans. R. Soc. Lond. B Biol. Sci. 364:2739–47
    [Google Scholar]
  23. 23. 
    Kuroda M, Katano H, Nakajima N, Tobiume M, Ainai A et al. 2010. Characterization of quasispecies of pandemic 2009 influenza A virus (A/H1N1/2009) by de novo sequencing using a next-generation DNA sequencer. PLOS ONE 5:e10256
    [Google Scholar]
  24. 24. 
    Nobusawa E, Sato K. 2006. Comparison of the mutation rates of human influenza A and B viruses. J. Virol. 80:3675–78
    [Google Scholar]
  25. 25. 
    Parvin JD, Moscona A, Pan WT, Leider JM, Palese P 1986. Measurement of the mutation rates of animal viruses: influenza A virus and poliovirus type 1. J. Virol. 59:377–83
    [Google Scholar]
  26. 26. 
    Ramakrishnan MA, Tu ZJ, Singh S, Chockalingam AK, Gramer MR et al. 2009. The feasibility of using high resolution genome sequencing of influenza A viruses to detect mixed infections and quasispecies. PLOS ONE 4:e7105
    [Google Scholar]
  27. 27. 
    Suárez P, Valcárcel J, Ortín J 1992. Heterogeneity of the mutation rates of influenza A viruses: isolation of mutator mutants. J. Virol. 66:2491–94
    [Google Scholar]
  28. 28. 
    Pauly MD, Procario MC, Lauring AS 2017. A novel twelve class fluctuation test reveals higher than expected mutation rates for influenza A viruses. eLife 6:e26437
    [Google Scholar]
  29. 29. 
    Octaviani CP, Ozawa M, Yamada S, Goto H, Kawaoka Y 2010. High level of genetic compatibility between swine-origin H1N1 and highly pathogenic avian H5N1 influenza viruses. J. Virol. 84:10918–22
    [Google Scholar]
  30. 30. 
    Li C, Hatta M, Nidom CA, Muramoto Y, Watanabe S et al. 2010. Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence. PNAS 107:4687–92
    [Google Scholar]
  31. 31. 
    Sun Y, Qin K, Wang J, Pu J, Tang Q et al. 2011. High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses. PNAS 108:4164–69
    [Google Scholar]
  32. 32. 
    Chen LM, Davis CT, Zhou H, Cox NJ, Donis RO 2008. Genetic compatibility and virulence of reassortants derived from contemporary avian H5N1 and human H3N2 influenza A viruses. PLOS Pathog 4:e1000072
    [Google Scholar]
  33. 33. 
    Ngunjiri JM, Buchek GM, Mohni KN, Sekellick MJ, Marcus PI 2013. Influenza virus subpopulations: exchange of lethal H5N1 virus NS for H1N1 virus NS triggers de novo generation of defective-interfering particles and enhances interferon-inducing particle efficiency. J. Interferon Cytokine Res. 33:99–107
    [Google Scholar]
  34. 34. 
    Murcia PR, Hughes J, Battista P, Lloyd L, Baillie GJ et al. 2012. Evolution of an Eurasian avian-like influenza virus in naive and vaccinated pigs. PLOS Pathog 8:e1002730
    [Google Scholar]
  35. 35. 
    Murcia PR, Baillie GJ, Stack JC, Jervis C, Elton D et al. 2013. Evolution of equine influenza virus in vaccinated horses. J. Virol. 87:84768–71
    [Google Scholar]
  36. 36. 
    Murcia PR, Baillie GJ, Daly J, Elton D, Jervis C et al. 2010. Intra- and interhost evolutionary dynamics of equine influenza virus. J. Virol. 84:6943–54
    [Google Scholar]
  37. 37. 
    Hoelzer K, Murcia PR, Baillie GJ, Wood JL, Metzger SM et al. 2010. Intrahost evolutionary dynamics of canine influenza virus in naive and partially immune dogs. J. Virol. 84:5329–35
    [Google Scholar]
  38. 38. 
    Hughes J, Allen RC, Baguelin M, Hampson K, Baillie GJ et al. 2012. Transmission of equine influenza virus during an outbreak is characterized by frequent mixed infections and loose transmission bottlenecks. PLOS Pathog 8:e1003081
    [Google Scholar]
  39. 39. 
    Bourret V, Croville G, Mansuy J-M, Mengelle C, Mariette J et al. 2015. Intra-host viral variability in children clinically infected with H1N1 2009 pandemic influenza. Infect. Genet. Evol. 33:47–54
    [Google Scholar]
  40. 40. 
    Nelson CW, Hughes AL. 2015. Within-host nucleotide diversity of virus populations: insights from next-generation sequencing. Infect. Genet. Evol. 30:1–7
    [Google Scholar]
  41. 41. 
    Cannon NA, Donlin MJ, Fan X, Aurora R, Tavis JE, Virahep-C Study Group 2008. Hepatitis C virus diversity and evolution in the full open-reading frame during antiviral therapy. PLOS ONE 3:e2123
    [Google Scholar]
  42. 42. 
    Hedskog C, Mild M, Jernberg J, Sherwood E, Bratt G et al. 2010. Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. PLOS ONE 5:e11345
    [Google Scholar]
  43. 43. 
    Le T, Chiarella J, Simen BB, Hanczaruk B, Egholm M et al. 2009. Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use. PLOS ONE 4:e6079
    [Google Scholar]
  44. 44. 
    Rozera G, Abbate I, Bruselles A, Vlassi C, D'Offizi G et al. 2009. Massively parallel pyrosequencing highlights minority variants in the HIV-1 env quasispecies deriving from lymphomonocyte sub-populations. Retrovirology 6:15
    [Google Scholar]
  45. 45. 
    Wang GP, Sherrill-Mix SA, Chang K-M, Quince C, Bushman FD 2010. Hepatitis C virus transmission bottlenecks analyzed by deep sequencing. J. Virol. 84:6218–28
    [Google Scholar]
  46. 46. 
    Heldt FS, Kupke SY, Dorl S, Reichl U, Frensing T 2015. Single-cell analysis and stochastic modelling unveil large cell-to-cell variability in influenza A virus infection. Nat. Commun. 6:8938
    [Google Scholar]
  47. 47. 
    Russell AB, Trapnell C, Bloom JD 2018. Extreme heterogeneity of influenza virus infection in single cells. eLife 7:e32303
    [Google Scholar]
  48. 48. 
    Russell AB, Elshina E, Kowalsky JR, te Velthuis AJ, Bloom JD 2019. Single-cell virus sequencing of influenza infections that trigger innate immunity. J. Virol. 93:e00500-19
    [Google Scholar]
  49. 49. 
    Sjaastad LE, Fay EJ, Fiege JK, Macchietto MG, Stone IA et al. 2018. Distinct antiviral signatures revealed by the magnitude and round of influenza virus replication in vivo. PNAS 115:9610–15
    [Google Scholar]
  50. 50. 
    von Magnus P. 1951. Propagation of the PR8 strain of influenza A virus in chick embryos. II. The formation of “incomplete” virus following inoculation of large doses of seed virus. Acta Pathol. Microbiol. Scand. 28:278–93
    [Google Scholar]
  51. 51. 
    von Magnus P. 1954. Incomplete forms of influenza virus. Adv. Virus Res. 2:59–79
    [Google Scholar]
  52. 52. 
    Nayak D, Chambers T, Akkina R 1985. Defective-interfering (DI) RNAs of influenza viruses: origin, structure, expression, and interference. Current Topics in Microbiology and Immunology M Cooper 103–51 Berlin/Heidelberg, Ger: Springer
    [Google Scholar]
  53. 53. 
    Tapia K, Kim W-k, Sun Y, Mercado-López X, Dunay E et al. 2013. Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity. PLOS Pathog 9:e1003703
    [Google Scholar]
  54. 54. 
    Saira K, Lin X, DePasse JV, Halpin R, Twaddle A et al. 2013. Sequence analysis of in vivo defective interfering-like RNA of influenza A H1N1 pandemic virus. J. Virol. 87:8064–74
    [Google Scholar]
  55. 55. 
    Marcus PI, Rojek JM, Sekellick MJ 2005. Interferon induction and/or production and its suppression by influenza A viruses. J. Virol. 79:2880–90
    [Google Scholar]
  56. 56. 
    Graef KM, Vreede FT, Lau YF, McCall AW, Carr SM et al. 2010. The PB2 subunit of the influenza virus RNA polymerase affects virulence by interacting with the mitochondrial antiviral signaling protein and inhibiting expression of beta interferon. J. Virol. 84:8433–45
    [Google Scholar]
  57. 57. 
    Iwai A, Shiozaki T, Kawai T, Akira S, Kawaoka Y et al. 2010. Influenza A virus polymerase inhibits type I interferon induction by binding to interferon beta promoter stimulator 1. J. Biol. Chem. 285:32064–74
    [Google Scholar]
  58. 58. 
    Zamarin D, García-Sastre A, Xiao X, Wang R, Palese P 2005. Influenza virus PB1-F2 protein induces cell death through mitochondrial ANT3 and VDAC1. PLOS Pathog 1:e4
    [Google Scholar]
  59. 59. 
    Dou D, Hernandez-Neuta I, Wang H, Ostbye H, Qian X et al. 2017. Analysis of IAV replication and co-infection dynamics by a versatile RNA viral genome labeling method. Cell Rep 20:251–63
    [Google Scholar]
  60. 60. 
    Fonville JM, Marshall N, Tao H, Steel J, Lowen AC 2015. Influenza virus reassortment is enhanced by semi-infectious particles but can be suppressed by defective interfering particles. PLOS Pathog 11:e1005204
    [Google Scholar]
  61. 61. 
    Fujii Y, Goto H, Watanabe T, Yoshida T, Kawaoka Y 2003. Selective incorporation of influenza virus RNA segments into virions. PNAS 100:2002–7
    [Google Scholar]
  62. 62. 
    Odagiri T, Tashiro M. 1997. Segment-specific noncoding sequences of the influenza virus genome RNA are involved in the specific competition between defective interfering RNA and its progenitor RNA segment at the virion assembly step. J. Virol. 71:2138–45
    [Google Scholar]
  63. 63. 
    Goto H, Muramoto Y, Noda T, Kawaoka Y 2013. The genome-packaging signal of the influenza A virus genome comprises a genome incorporation signal and a genome-bundling signal. J. Virol. 87:11316–22
    [Google Scholar]
  64. 64. 
    Hutchinson EC, von Kirchbach JC, Gog JR, Digard P 2010. Genome packaging in influenza A virus. J. Gen. Virol. 91:313–28
    [Google Scholar]
  65. 65. 
    Nakatsu S, Sagara H, Sakai-Tagawa Y, Sugaya N, Noda T, Kawaoka Y 2016. Complete and incomplete genome packaging of influenza A and B viruses. mBio 7:e01248-16
    [Google Scholar]
  66. 66. 
    Isel C, Munier S, Naffakh N 2016. Experimental approaches to study genome packaging of influenza A viruses. Viruses 8:218
    [Google Scholar]
  67. 67. 
    Brooke CB, Ince WL, Wei J, Bennink JR, Yewdell JW 2014. Influenza A virus nucleoprotein selectively decreases neuraminidase gene-segment packaging while enhancing viral fitness and transmissibility. PNAS 111:16854–59
    [Google Scholar]
  68. 68. 
    Gultyaev AP, Tsyganov-Bodounov A, Spronken MI, van der Kooij S, Fouchier RA, Olsthoorn RC 2014. RNA structural constraints in the evolution of the influenza A virus genome NP segment. RNA Biol 11:942–52
    [Google Scholar]
  69. 69. 
    Hutchinson EC, Wise HM, Kudryavtseva K, Curran MD, Digard P 2009. Characterisation of influenza A viruses with mutations in segment 5 packaging signals. Vaccine 27:6270–75
    [Google Scholar]
  70. 70. 
    Kupke SY, Riedel D, Frensing T, Zmora P, Reichl U 2019. A novel type of influenza A virus-derived defective interfering particle with nucleotide substitutions in its genome. J. Virol. 93:4e01786-18
    [Google Scholar]
  71. 71. 
    Brooke CB. 2014. Biological activities of “noninfectious” influenza A virus particles. Future Virol 9:41–51
    [Google Scholar]
  72. 72. 
    Wang Z, Robb NC, Lenz E, Wolff T, Fodor E, Pleschka S 2010. NS reassortment of an H7-type highly pathogenic avian influenza virus affects its propagation by altering the regulation of viral RNA production and antiviral host response. J. Virol. 84:11323–35
    [Google Scholar]
  73. 73. 
    Fodor E, Mingay LJ, Crow M, Deng T, Brownlee GG 2003. A single amino acid mutation in the PA subunit of the influenza virus RNA polymerase promotes the generation of defective interfering RNAs. J. Virol. 77:5017–20
    [Google Scholar]
  74. 74. 
    Vasilijevic J, Zamarreño N, Oliveros JC, Rodriguez-Frandsen A, Gómez G et al. 2017. Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients. PLOS Pathog 13:e1006650
    [Google Scholar]
  75. 75. 
    Odagiri T, Tobita K. 1990. Mutation in NS2, a nonstructural protein of influenza A virus, extragenically causes aberrant replication and expression of the PA gene and leads to generation of defective interfering particles. PNAS 87:5988–92
    [Google Scholar]
  76. 76. 
    Pérez-Cidoncha M, Killip MJ, Oliveros JC, Asensio VJ, Fernández Y et al. 2014. An unbiased genetic screen reveals the polygenic nature of the influenza virus anti-interferon response. J. Virol. 88:4632–46
    [Google Scholar]
  77. 77. 
    Pflug A, Guilligay D, Reich S, Cusack S 2014. Structure of influenza A polymerase bound to the viral RNA promoter. Nature 516:355–60
    [Google Scholar]
  78. 78. 
    Jorba N, Coloma R, Ortín J 2009. Genetic trans-complementation establishes a new model for influenza virus RNA transcription and replication. PLOS Pathog 5:e1000462
    [Google Scholar]
  79. 79. 
    Chang S, Sun D, Liang H, Wang J, Li J et al. 2015. Cryo-EM structure of influenza virus RNA polymerase complex at 4.3 Å resolution. Mol. Cell 57:925–35
    [Google Scholar]
  80. 80. 
    Lenartowicz E, Kesy J, Ruszkowska A, Soszynska-Jozwiak M, Michalak P et al. 2016. Self-folding of naked segment 8 genomic RNA of influenza A virus. PLOS ONE 11:e0148281
    [Google Scholar]
  81. 81. 
    Williams GD, Townsend D, Wylie KM, Kim PJ, Amarasinghe GK et al. 2018. Nucleotide resolution mapping of influenza A virus nucleoprotein-RNA interactions reveals RNA features required for replication. Nat. Commun. 9:465
    [Google Scholar]
  82. 82. 
    Sekellick MJ, Carra SA, Bowman A, Hopkins DA, Marcus PI 2000. Transient resistance of influenza virus to interferon action attributed to random multiple packaging and activity of NS genes. J. Interferon Cytokine Res. 20:963–70
    [Google Scholar]
  83. 83. 
    Sanjuán R. 2017. Collective infectious units in viruses. Trends Microbiol 25:402–12
    [Google Scholar]
  84. 84. 
    Sanjuan R. 2018. Collective properties of viral infectivity. Curr. Opin. Virol. 33:1–6
    [Google Scholar]
  85. 85. 
    Luo W, Zhang J, Liang L, Wang G, Li Q et al. 2018. Phospholipid scramblase 1 interacts with influenza A virus NP, impairing its nuclear import and thereby suppressing virus replication. PLOS Pathog 14:e1006851
    [Google Scholar]
  86. 86. 
    Götz V, Magar L, Dornfeld D, Giese S, Pohlmann A et al. 2016. Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import. Sci. Rep. 6:23138
    [Google Scholar]
  87. 87. 
    Vahey MD, Fletcher DA. 2019. Low-fidelity assembly of influenza A virus promotes escape from host cells. Cell 176:281–94.e19
    [Google Scholar]
  88. 88. 
    Amini-Bavil-Olyaee S, Choi YJ, Lee JH, Shi M, Huang IC et al. 2013. The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry. Cell Host Microbe 13:452–64
    [Google Scholar]
  89. 89. 
    Bajimaya S, Frankl T, Hayashi T, Takimoto T 2017. Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses. Virology 510:234–41
    [Google Scholar]
  90. 90. 
    Roberts PC, Lamb RA, Compans RW 1998. The M1 and M2 proteins of influenza A virus are important determinants in filamentous particle formation. Virology 240:127–37
    [Google Scholar]
  91. 91. 
    Rossman JS, Lamb RA. 2011. Influenza virus assembly and budding. Virology 411:229–36
    [Google Scholar]
  92. 92. 
    Burleigh LM, Calder LJ, Skehel JJ, Steinhauer DA 2005. Influenza A viruses with mutations in the m1 helix six domain display a wide variety of morphological phenotypes. J. Virol. 79:1262–70
    [Google Scholar]
  93. 93. 
    Marcus PI, Ngunjiri JM, Sekellick MJ, Wang L, Lee CW 2010. In vitro analysis of virus particle subpopulations in candidate live-attenuated influenza vaccines distinguishes effective from ineffective vaccines. J. Virol. 84:10974–81
    [Google Scholar]
  94. 94. 
    Ngunjiri JM, Ali A, Boyaka P, Marcus PI, Lee CW 2015. In vivo assessment of NS1-truncated influenza virus with a novel SLSYSINWRH motif as a self-adjuvanting live attenuated vaccine. PLOS ONE 10:e0118934
    [Google Scholar]
  95. 95. 
    Dimmock NJ, Rainsford EW, Scott PD, Marriott AC 2008. Influenza virus protecting RNA: an effective prophylactic and therapeutic antiviral. J. Virol. 82:8570–78
    [Google Scholar]
  96. 96. 
    Easton AJ, Scott PD, Edworthy NL, Meng B, Marriott AC, Dimmock NJ 2011. A novel broad-spectrum treatment for respiratory virus infections: Influenza-based defective interfering virus provides protection against pneumovirus infection in vivo. Vaccine 29:2777–84
    [Google Scholar]
  97. 97. 
    Wasik MA, Eichwald L, Genzel Y, Reichl U 2018. Cell culture-based production of defective interfering particles for influenza antiviral therapy. Appl. Microbiol. Biotechnol. 102:1167–77
    [Google Scholar]
  98. 98. 
    Dimmock NJ, Easton AJ. 2014. Defective interfering influenza virus RNAs: Time to reevaluate their clinical potential as broad-spectrum antivirals?. J. Virol. 88:5217–27
    [Google Scholar]
  99. 99. 
    Marriott AC, Dimmock NJ. 2010. Defective interfering viruses and their potential as antiviral agents. Rev. Med. Virol. 20:51–62
    [Google Scholar]
  100. 100. 
    Frensing T. 2015. Defective interfering viruses and their impact on vaccines and viral vectors. Biotechnol. J. 10:681–89
    [Google Scholar]
  101. 101. 
    Barrett AD, Dimmock NJ. 1986. Defective interfering viruses and infections of animals. Curr. Top. Microbiol. Immunol. 128:55–84
    [Google Scholar]
  102. 102. 
    Duhaut SD, Dimmock NJ. 1998. Heterologous protection of mice from a lethal human H1N1 influenza A virus infection by H3N8 equine defective interfering virus: comparison of defective RNA sequences isolated from the DI inoculum and mouse lung. Virology 248:241–53
    [Google Scholar]
  103. 103. 
    Jennings PA, Finch JT, Winter G, Robertson JS 1983. Does the higher order structure of the influenza virus ribonucleoprotein guide sequence rearrangements in influenza viral RNA?. Cell 34:619–27
    [Google Scholar]
  104. 104. 
    Nayak DP, Tobita K, Janda JM, Davis AR, De BK 1978. Homologous interference mediated by defective interfering influenza virus derived from a temperature-sensitive mutant of influenza virus. J. Virol. 28:375–86
    [Google Scholar]
  105. 105. 
    Ngunjiri JM, Lee C-W, Ali A, Marcus PI 2012. Influenza virus interferon-inducing particle efficiency is reversed in avian and mammalian cells, and enhanced in cells co-infected with defective-interfering particles. J. Interferon Cytokine Res. 32:280–85
    [Google Scholar]
  106. 106. 
    Belton J-M, McCord RP, Gibcus JH, Naumova N, Zhan Y, Dekker J 2012. Hi–C: a comprehensive technique to capture the conformation of genomes. Methods 58:268–76
    [Google Scholar]
  107. 107. 
    Churchman LS, Weissman JS. 2011. Nascent transcript sequencing visualizes transcription at nucleotide resolution. Nature 469:368–73
    [Google Scholar]
  108. 108. 
    Mazur I, Anhlan D, Mitzner D, Wixler L, Schubert U, Ludwig S 2008. The proapoptotic influenza A virus protein PB1-F2 regulates viral polymerase activity by interaction with the PB1 protein. Cell. Microbiol. 10:1140–52
    [Google Scholar]
  109. 109. 
    Stray SJ, Air GM. 2001. Apoptosis by influenza viruses correlates with efficiency of viral mRNA synthesis. Virus Res 77:3–17
    [Google Scholar]
  110. 110. 
    Zhirnov OP, Konakova TE, Wolff T, Klenk HD 2002. NS1 protein of influenza A virus down-regulates apoptosis. J. Virol. 76:1617–25
    [Google Scholar]
  111. 111. 
    Min J-Y, Li S, Sen GC, Krug RM 2007. A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesis. Virology 363:236–43
    [Google Scholar]
  112. 112. 
    Iwai A, Shiozaki T, Miyazaki T 2013. Relevance of signaling molecules for apoptosis induction on influenza A virus replication. Biochem. Biophys. Res. Commun. 441:531–37
    [Google Scholar]
  113. 113. 
    Malinoski CP, Marcus PI. 2013. Influenza virus subpopulations: Interferon induction-suppressing particles require expression of NS1 and act globally in cells; UV irradiation of interferon-inducing particles blocks global shut-off and enhances interferon production. J. Interferon Cytokine Res. 33:72–79
    [Google Scholar]
  114. 114. 
    Akkina RK, Chambers TM, Nayak DP 1984. Mechanism of interference by defective-interfering particles of influenza virus: differential reduction of intracellular synthesis of specific polymerase proteins. Virus Res 1:687–702
    [Google Scholar]
  115. 115. 
    Baum A, Sachidanandam R, García-Sastre A 2010. Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing. PNAS 107:16303–8
    [Google Scholar]
  116. 116. 
    Hayashi T, Watanabe C, Suzuki Y, Tanikawa T, Uchida Y, Saito T 2014. Chicken MDA5 senses short double-stranded RNA with implications for antiviral response against avian influenza viruses in chicken. J. Innate Immun. 6:58–71
    [Google Scholar]
  117. 117. 
    Medina RA, García-Sastre A. 2011. Influenza A viruses: new research developments. Nat. Rev. Microbiol. 9:590–603
    [Google Scholar]
  118. 118. 
    Bean W, Kawaoka Y, Wood J, Pearson J, Webster R 1985. Characterization of virulent and avirulent A/chicken/Pennsylvania/83 influenza A viruses: potential role of defective interfering RNAs in nature. J. Virol. 54:151–60
    [Google Scholar]
  119. 119. 
    Chambers TM, Webster RG. 1987. Defective interfering virus associated with A/Chicken/Pennsylvania/83 influenza virus. J. Virol. 61:1517–23
    [Google Scholar]
  120. 120. 
    DeJesus E, Costa-Hurtado M, Smith D, Lee D-H, Spackman E et al. 2016. Changes in adaptation of H5N2 highly pathogenic avian influenza H5 clade 2.3.4.4 viruses in chickens and mallards. Virology 499:52–64
    [Google Scholar]
  121. 121. 
    Spackman E, Pantin-Jackwood MJ, Kapczynski DR, Swayne DE, Suarez DL 2016. H5N2 highly pathogenic avian influenza viruses from the US 2014–2015 outbreak have an unusually long pre-clinical period in turkeys. BMC Vet. Res. 12:260
    [Google Scholar]
  122. 122. 
    Pantin-Jackwood MJ, Stephens CB, Bertran K, Swayne DE, Spackman E 2017. The pathogenesis of H7N8 low and highly pathogenic avian influenza viruses from the United States 2016 outbreak in chickens, turkeys and mallards. PLOS ONE 12:e0177265
    [Google Scholar]
  123. 123. 
    Bertran K, Lee D-H, Criado MF, Smith D, Swayne DE, Pantin-Jackwood MJ 2018. Pathobiology of Tennessee 2017 H7N9 low and high pathogenicity avian influenza viruses in commercial broiler breeders and specific pathogen free layer chickens. Vet. Res. 49:82
    [Google Scholar]
  124. 124. 
    Noble S, McLain L, Dimmock NJ 2004. Interfering vaccine: a novel antiviral that converts a potentially virulent infection into one that is subclinical and immunizing. Vaccine 22:3018–25
    [Google Scholar]
  125. 125. 
    Mann A, Marriott AC, Balasingam S, Lambkin R, Oxford JS, Dimmock NJ 2006. Interfering vaccine (defective interfering influenza A virus) protects ferrets from influenza, and allows them to develop solid immunity to reinfection. Vaccine 24:4290–96
    [Google Scholar]
  126. 126. 
    Dimmock NJ, Beck S, McLain L 1986. Protection of mice from lethal influenza: evidence that defective interfering virus modulates the immune response and not virus multiplication. J. Gen. Virol. 67:839–50
    [Google Scholar]
  127. 127. 
    Cauthen AN, Swayne DE, Sekellick MJ, Marcus PI, Suarez DL 2007. Amelioration of influenza virus pathogenesis in chickens attributed to the enhanced interferon-inducing capacity of a virus with a truncated NS1 gene. J. Virol. 81:1838–47
    [Google Scholar]
  128. 128. 
    Kayamuro H, Yoshioka Y, Abe Y, Arita S, Katayama K et al. 2010. Interleukin-1 family cytokines as mucosal vaccine adjuvants for induction of protective immunity against influenza virus. J. Virol. 84:12703–12
    [Google Scholar]
  129. 129. 
    Staats HF, Bradney CP, Gwinn WM, Jackson SS, Sempowski GD et al. 2001. Cytokine requirements for induction of systemic and mucosal CTL after nasal immunization. J. Immunol. 167:5386–94
    [Google Scholar]
  130. 130. 
    Bracci L, Canini I, Venditti M, Spada M, Puzelli S et al. 2006. Type I IFN as a vaccine adjuvant for both systemic and mucosal vaccination against influenza virus. Vaccine 24:Suppl. 2S56–57
    [Google Scholar]
  131. 131. 
    Bracci L, Canini I, Puzelli S, Sestili P, Venditti M et al. 2005. Type I IFN is a powerful mucosal adjuvant for a selective intranasal vaccination against influenza virus in mice and affects antigen capture at mucosal level. Vaccine 23:2994–3004
    [Google Scholar]
  132. 132. 
    Proietti E, Bracci L, Puzelli S, Di Pucchio T, Sestili P et al. 2002. Type I IFN as a natural adjuvant for a protective immune response: lessons from the influenza vaccine model. J. Immunol. 169:375–83
    [Google Scholar]
  133. 133. 
    Marcus PI, Girshick T, van der Heide L, Sekellick MJ 2007. Super-sentinel chickens and detection of low-pathogenicity influenza virus. Emerg. Infect. Dis. 13:1608–10
    [Google Scholar]
  134. 134. 
    Jang H, Ngunjiri JM, Lee CW 2016. Association between interferon response and protective efficacy of NS1-truncated mutants as influenza vaccine candidates in chickens. PLOS ONE 11:e0156603
    [Google Scholar]
  135. 135. 
    Ghorbani A, Ngunjiri JM, Xia M, Elaish M, Jang H et al. 2019. Heterosubtypic protection against avian influenza virus by live attenuated and chimeric norovirus P-particle-M2e vaccines in chickens. Vaccine 37:1356–64
    [Google Scholar]
  136. 136. 
    Jang H, Elaish M, KC M, Abundo MC, Ghorbani A et al. 2018. Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens. PLOS ONE 13:e0195285
    [Google Scholar]
  137. 137. 
    Wang L, Suarez D, Pantin-Jackwood M, Mibayashi M, García-Sastre A et al. 2008. Characterization of influenza virus variants with different sizes of the non-structural (NS) genes and their potential as a live influenza vaccine in poultry. Vaccine 26:3580–86
    [Google Scholar]
  138. 138. 
    Hinshaw VS, Olsen CW, Dybdahl-Sissoko N, Evans D 1994. Apoptosis: a mechanism of cell killing by influenza A and B viruses. J. Virol. 68:3667–73
    [Google Scholar]
  139. 139. 
    Fujimoto I, Pan J, Takizawa T, Nakanishi Y 2000. Virus clearance through apoptosis-dependent phagocytosis of influenza A virus-infected cells by macrophages. J. Virol. 74:3399–403
    [Google Scholar]
  140. 140. 
    Hashimoto Y, Moki T, Takizawa T, Shiratsuchi A, Nakanishi Y 2007. Evidence for phagocytosis of influenza virus-infected, apoptotic cells by neutrophils and macrophages in mice. J. Immunol. 178:2448–57
    [Google Scholar]
  141. 141. 
    Kagan JC, Iwasaki A. 2012. Phagosome as the organelle linking innate and adaptive immunity. Traffic 13:1053–61
    [Google Scholar]
  142. 142. 
    Richt JA, García-Sastre A. 2009. Attenuated influenza virus vaccines with modified NS1 proteins. Curr. Top. Microbiol. Immunol. 333:177–95
    [Google Scholar]
  143. 143. 
    Steel J, Lowen AC, Pena L, Angel M, Solórzano A et al. 2009. Live attenuated influenza viruses containing NS1 truncations as vaccine candidates against H5N1 highly pathogenic avian influenza. J. Virol. 83:1742–53
    [Google Scholar]
  144. 144. 
    Frensing T, Pflugmacher A, Bachmann M, Peschel B, Reichl U 2014. Impact of defective interfering particles on virus replication and antiviral host response in cell culture-based influenza vaccine production. Appl. Microbiol. Biotechnol. 98:8999–9008
    [Google Scholar]
  145. 145. 
    Rüdiger D, Kupke SY, Laske T, Zmora P, Reichl U 2019. Multiscale modeling of influenza A virus replication in cell cultures predicts infection dynamics for highly different infection conditions. PLOS Comput. Biol. 15:e1006819
    [Google Scholar]
  146. 146. 
    Gould PS, Easton AJ, Dimmock NJ 2017. Live attenuated influenza vaccine contains substantial and unexpected amounts of defective viral genomic RNA. Viruses 9:269
    [Google Scholar]
/content/journals/10.1146/annurev-animal-021419-083756
Loading
/content/journals/10.1146/annurev-animal-021419-083756
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