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Semin Respir Crit Care Med 2016; 37(04): 487-500
DOI: 10.1055/s-0036-1584801
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Human Influenza Virus Infections

Christin Peteranderl
1   Department of Internal Medicine II, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
,
Susanne Herold
1   Department of Internal Medicine II, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
,
Carole Schmoldt
1   Department of Internal Medicine II, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 August 2016 (online)

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Abstract

Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection.

Keywords

influenza virus - seasonal - pandemic - pneumonia - lung injury - ARDS - vaccination - antiviral therapy
 

  • References

  • 1 Schmolke M, García-Sastre A. Evasion of innate and adaptive immune responses by influenza A virus. Cell Microbiol 2010; 12 (7) 873-880
    CrossrefPubMedGoogle Scholar
  • 2 Vossen MT, Westerhout EM, Söderberg-Nauclér C, Wiertz EJ. Viral immune evasion: a masterpiece of evolution. Immunogenetics 2002; 54 (8) 527-542
    CrossrefPubMedGoogle Scholar
  • 3 Abdel-Ghafar AN, Chotpitayasunondh T, Gao Z , et al; Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus. Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med 2008; 358 (3) 261-273
    CrossrefPubMedGoogle Scholar
  • 4 Ungchusak K, Auewarakul P, Dowell SF , et al. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med 2005; 352 (4) 333-340
    CrossrefPubMedGoogle Scholar
  • 5 Wu Y, Wu Y, Tefsen B, Shi Y, Gao GF. Bat-derived influenza-like viruses H17N10 and H18N11. Trends Microbiol 2014; 22 (4) 183-191
    CrossrefPubMedGoogle Scholar
  • 6 García-Sastre A. The neuraminidase of bat influenza viruses is not a neuraminidase. Proc Natl Acad Sci U S A 2012; 109 (46) 18635-18636
    CrossrefPubMedGoogle Scholar
  • 7 Lowen AC, Mubareka S, Steel J, Palese P. Influenza virus transmission is dependent on relative humidity and temperature. PLoS Pathog 2007; 3 (10) 1470-1476
    PubMedGoogle Scholar
  • 8 Bedford T, Riley S, Barr IG , et al. Global circulation patterns of seasonal influenza viruses vary with antigenic drift. Nature 2015; 523 (7559) 217-220
    CrossrefPubMedGoogle Scholar
  • 9 Rambaut A, Pybus OG, Nelson MI, Viboud C, Taubenberger JK, Holmes EC. The genomic and epidemiological dynamics of human influenza A virus. Nature 2008; 453 (7195) 615-619
    CrossrefPubMedGoogle Scholar
  • 10 World Health Organization Fact Sheet on Influenza; 2014. Available at: http://www.who.int/mediacentre/factsheets/fs211/en/ . Accessed August 18, 2015
    PubMedGoogle Scholar
  • 11 Ortiz JR, Neuzil KM, Rue TC , et al. Population-based incidence estimates of influenza-associated respiratory failure hospitalizations, 2003 to 2009. Am J Respir Crit Care Med 2013; 188 (6) 710-715
    CrossrefPubMedGoogle Scholar
  • 12 Molinari NA, Ortega-Sanchez IR, Messonnier ML , et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine 2007; 25 (27) 5086-5096
    CrossrefPubMedGoogle Scholar
  • 13 Cox NJ, Subbarao K. Global epidemiology of influenza: past and present. Annu Rev Med 2000; 51: 407-421
    CrossrefPubMedGoogle Scholar
  • 14 Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ, Fukuda K. Pandemic versus epidemic influenza mortality: a pattern of changing age distribution. J Infect Dis 1998; 178 (1) 53-60
    CrossrefPubMedGoogle Scholar
  • 15 Taubenberger JK. The origin and virulence of the 1918 “Spanish” influenza virus. Proc Am Philos Soc 2006; 150 (1) 86-112
    PubMedGoogle Scholar
  • 16 Miller MA, Viboud C, Balinska M, Simonsen L. The signature features of influenza pandemics—implications for policy. N Engl J Med 2009; 360 (25) 2595-2598
    CrossrefPubMedGoogle Scholar
  • 17 Libster R, Coviello S, Cavalieri ML , et al. Pediatric hospitalizations due to influenza in 2010 in Argentina. N Engl J Med 2010; 363 (25) 2472-2473
    CrossrefPubMedGoogle Scholar
  • 18 Tanner WD, Toth DJ, Gundlapalli AV. The pandemic potential of avian influenza A(H7N9) virus: a review. Epidemiol Infect 2015; 143 (16) 3359-3374
    CrossrefPubMedGoogle Scholar
  • 19 Pappaioanou M, Gramer M. Lessons from pandemic H1N1 2009 to improve prevention, detection, and response to influenza pandemics from a One Health perspective. ILAR J 2010; 51 (3) 268-280
    CrossrefPubMedGoogle Scholar
  • 20 Goldstein T, Mena I, Anthony SJ , et al. Pandemic H1N1 influenza isolated from free-ranging Northern Elephant Seals in 2010 off the central California coast. PLoS ONE 2013; 8 (5) e62259
    CrossrefPubMedGoogle Scholar
  • 21 Parrish CR, Murcia PR, Holmes EC. Influenza virus reservoirs and intermediate hosts: dogs, horses, and new possibilities for influenza virus exposure of humans. J Virol 2015; 89 (6) 2990-2994
    CrossrefPubMedGoogle Scholar
  • 22 Uyeki TM, Cox NJ. Global concerns regarding novel influenza A (H7N9) virus infections. N Engl J Med 2013; 368 (20) 1862-1864
    CrossrefPubMedGoogle Scholar
  • 23 Simon PF, McCorrister S, Hu P , et al. Highly pathogenic H5N1 and novel H7N9 influenza A viruses induce more profound proteomic host responses than seasonal and pandemic H1N1 strains. J Proteome Res 2015; 14 (11) 4511-4523
    CrossrefPubMedGoogle Scholar
  • 24 H5N1 Avian Flu (H5N1 Bird Flu) Available at: http://wwwflugov/about_the_flu/h5n1/indexhtml . Accessed August 21, 2015
    PubMed
  • 25 WHO. Cumulative number of confirmed human cases for avian influenza A(H5N1) reported to WHO 2003–2015. Available at: http://www.who.int/influenza/human_animal_interface/EN_GIP_20150904cumulativeNumberH5N1cases.pdf . Accessed August 21, 2015
    PubMedGoogle Scholar
  • 26 Areechokchai D, Jiraphongsa C, Laosiritaworn Y, Hanshaoworakul W, O'Reilly M ; Centers for Disease Control and Prevention (CDC). Investigation of avian influenza (H5N1) outbreak in humans—Thailand, 2004. MMWR Suppl 2006; 55 (Suppl. 01) 3-6
    PubMedGoogle Scholar
  • 27 Chen Y, Liang W, Yang S , et al. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Lancet 2013; 381 (9881) 1916-1925
    CrossrefPubMedGoogle Scholar
  • 28 WHO. Who Risk Assessment of Human infections with avian influenza A (H7N9) Virus. Available at: http://www.who.int/influenza/human_animal_interface/influenza_h7n9/RiskAssessment_H7N9_23Feb20115.pdf?ua=1 . Accessed August 21, 2015
    PubMedGoogle Scholar
  • 29 Xiong X, Martin SR, Haire LF , et al. Receptor binding by an H7N9 influenza virus from humans. Nature 2013; 499 (7459) 496-499
    CrossrefPubMedGoogle Scholar
  • 30 Chan MC, Chan RW, Chan LL , et al. Tropism and innate host responses of a novel avian influenza A H7N9 virus: an analysis of ex-vivo and in-vitro cultures of the human respiratory tract. Lancet Respir Med 2013; 1 (7) 534-542
    CrossrefPubMedGoogle Scholar
  • 31 Ito T, Couceiro JN, Kelm S , et al. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J Virol 1998; 72 (9) 7367-7373
    PubMedGoogle Scholar
  • 32 Janke BH. Influenza A virus infections in swine: pathogenesis and diagnosis. Vet Pathol 2014; 51 (2) 410-426
    CrossrefPubMedGoogle Scholar
  • 33 Trock SC, Burke SA, Cox NJ. Development of framework for assessing influenza virus pandemic risk. Emerg Infect Dis 2015; 21 (8) 1372-1378
    CrossrefPubMedGoogle Scholar
  • 34 Valleron AJ, Cori A, Valtat S, Meurisse S, Carrat F, Boëlle PY. Transmissibility and geographic spread of the 1889 influenza pandemic. Proc Natl Acad Sci U S A 2010; 107 (19) 8778-8781
    CrossrefPubMedGoogle Scholar
  • 35 Trotter Jr Y, Dunn FL, Drachman RH, Henderson DA, Pizzi M, Langmuir AD. Asian influenza in the United States, 1957-1958. Am J Hyg 1959; 70 (1) 34-50
    PubMedGoogle Scholar
  • 36 Xu R, McBride R, Paulson JC, Basler CF, Wilson IA. Structure, receptor binding, and antigenicity of influenza virus hemagglutinins from the 1957 H2N2 pandemic. J Virol 2010; 84 (4) 1715-1721
    CrossrefPubMedGoogle Scholar
  • 37 Lindsay Jr MI, Herrmann Jr EC, Morrow Jr GW, Brown Jr AL. Hong Kong influenza: clinical, microbiologic, and pathologic features in 127 cases. JAMA 1970; 214 (10) 1825-1832
    CrossrefPubMedGoogle Scholar
  • 38 Taubenberger JK, Morens DM. 1918 Influenza: the mother of all pandemics. Emerg Infect Dis 2006; 12 (1) 15-22
    CrossrefPubMedGoogle Scholar
  • 39 Sheng ZM, Chertow DS, Ambroggio X , et al. Autopsy series of 68 cases dying before and during the 1918 influenza pandemic peak. Proc Natl Acad Sci U S A 2011; 108 (39) 16416-16421
    CrossrefPubMedGoogle Scholar
  • 40 Perrone LA, Plowden JK, García-Sastre A, Katz JM, Tumpey TM. H5N1 and 1918 pandemic influenza virus infection results in early and excessive infiltration of macrophages and neutrophils in the lungs of mice. PLoS Pathog 2008; 4 (8) e1000115
    CrossrefPubMedGoogle Scholar
  • 41 Dawood FS, Iuliano AD, Reed C , et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis 2012; 12 (9) 687-695
    CrossrefPubMedGoogle Scholar
  • 42 Mukherjee S, Vipat VC, Mishra AC, Pawar SD, Chakrabarti AK. Pandemic (H1N1) 2009 influenza virus induces weaker host immune responses in vitro: a possible mechanism of high transmissibility. Virol J 2011; 8: 140
    CrossrefPubMedGoogle Scholar
  • 43 Rust MJ, Lakadamyali M, Zhang F, Zhuang X. Assembly of endocytic machinery around individual influenza viruses during viral entry. Nat Struct Mol Biol 2004; 11 (6) 567-573
    CrossrefPubMedGoogle Scholar
  • 44 Pinto LH, Lamb RA. The M2 proton channels of influenza A and B viruses. J Biol Chem 2006; 281 (14) 8997-9000
    CrossrefPubMedGoogle Scholar
  • 45 Mair CM, Ludwig K, Herrmann A, Sieben C. Receptor binding and pH stability - how influenza A virus hemagglutinin affects host-specific virus infection. Biochim Biophys Acta 2014; 1838 (4) 1153-1168
    CrossrefPubMedGoogle Scholar
  • 46 Zaraket H, Bridges OA, Russell CJ. The pH of activation of the hemagglutinin protein regulates H5N1 influenza virus replication and pathogenesis in mice. J Virol 2013; 87 (9) 4826-4834
    CrossrefPubMedGoogle Scholar
  • 47 Resa-Infante P, Thieme R, Ernst T , et al. Importin-α7 is required for enhanced influenza A virus replication in the alveolar epithelium and severe lung damage in mice. J Virol 2014; 88 (14) 8166-8179
    CrossrefPubMedGoogle Scholar
  • 48 Gabriel G, Klingel K, Otte A , et al. Differential use of importin-α isoforms governs cell tropism and host adaptation of influenza virus. Nat Commun 2011; 2: 156
    CrossrefPubMedGoogle Scholar
  • 49 Gabriel G, Herwig A, Klenk HD. Interaction of polymerase subunit PB2 and NP with importin alpha1 is a determinant of host range of influenza A virus. PLoS Pathog 2008; 4 (2) e11
    CrossrefPubMedGoogle Scholar
  • 50 Massin P, van der Werf S, Naffakh N. Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses. J Virol 2001; 75 (11) 5398-5404
    CrossrefPubMedGoogle Scholar
  • 51 Rossman JS, Lamb RA. Influenza virus assembly and budding. Virology 2011; 411 (2) 229-236
    CrossrefPubMedGoogle Scholar
  • 52 Wagner R, Matrosovich M, Klenk HD. Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol 2002; 12 (3) 159-166
    CrossrefPubMedGoogle Scholar
  • 53 Baigent SJ, McCauley JW. Influenza type A in humans, mammals and birds: determinants of virus virulence, host-range and interspecies transmission. BioEssays 2003; 25 (7) 657-671
    CrossrefPubMedGoogle Scholar
  • 54 Scull MA, Gillim-Ross L, Santos C , et al. Avian Influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways. PLoS Pathog 2009; 5 (5) e1000424
    CrossrefPubMedGoogle Scholar
  • 55 Tscherne DM, García-Sastre A. Virulence determinants of pandemic influenza viruses. J Clin Invest 2011; 121 (1) 6-13
    CrossrefPubMedGoogle Scholar
  • 56 Mänz B, Schwemmle M, Brunotte L. Adaptation of avian influenza A virus polymerase in mammals to overcome the host species barrier. J Virol 2013; 87 (13) 7200-7209
    CrossrefPubMedGoogle Scholar
  • 57 Scholtissek C, Rohde W, Von Hoyningen V, Rott R. On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology 1978; 87 (1) 13-20
    CrossrefPubMedGoogle Scholar
  • 58 Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature 2005; 437 (7060) 889-893
    CrossrefPubMedGoogle Scholar
  • 59 Liu Q, Lu L, Sun Z, Chen GW, Wen Y, Jiang S. Genomic signature and protein sequence analysis of a novel influenza A (H7N9) virus that causes an outbreak in humans in China. Microbes Infect 2013; 15 (6–7) 432-439
    CrossrefPubMedGoogle Scholar
  • 60 Long JS, Howard WA, Núñez A , et al. The effect of the PB2 mutation 627K on highly pathogenic H5N1 avian influenza virus is dependent on the virus lineage. J Virol 2013; 87 (18) 9983-9996
    CrossrefPubMedGoogle Scholar
  • 61 Salomon R, Franks J, Govorkova EA , et al. The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. J Exp Med 2006; 203 (3) 689-697
    CrossrefPubMedGoogle Scholar
  • 62 Mukherjee S, Majumdar S, Vipat VC, Mishra AC, Chakrabarti AK. Non structural protein of avian influenza A (H11N1) virus is a weaker suppressor of immune responses but capable of inducing apoptosis in host cells. Virol J 2012; 9: 149
    CrossrefPubMedGoogle Scholar
  • 63 Munier S, Larcher T, Cormier-Aline F , et al. A genetically engineered waterfowl influenza virus with a deletion in the stalk of the neuraminidase has increased virulence for chickens. J Virol 2010; 84 (2) 940-952
    CrossrefPubMedGoogle Scholar
  • 64 Herold S, Becker C, Ridge KM, Budinger GR. Influenza virus-induced lung injury: pathogenesis and implications for treatment. Eur Respir J 2015; 45 (5) 1463-1478
    CrossrefPubMedGoogle Scholar
  • 65 Solórzano A, Webby RJ, Lager KM, Janke BH, García-Sastre A, Richt JA. Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs. J Virol 2005; 79 (12) 7535-7543
    CrossrefPubMedGoogle Scholar
  • 66 Wang X, Li M, Zheng H , et al. Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon. J Virol 2000; 74 (24) 11566-11573
    CrossrefPubMedGoogle Scholar
  • 67 Fouchier RA, Schneeberger PM, Rozendaal FW , et al. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci U S A 2004; 101 (5) 1356-1361
    CrossrefPubMedGoogle Scholar
  • 68 Steinhauer DA. Role of hemagglutinin cleavage for the pathogenicity of influenza virus. Virology 1999; 258 (1) 1-20
    CrossrefPubMedGoogle Scholar
  • 69 Klenk HD, Garten W. Host cell proteases controlling virus pathogenicity. Trends Microbiol 1994; 2 (2) 39-43
    CrossrefPubMedGoogle Scholar
  • 70 Tate MD, Job ER, Deng YM, Gunalan V, Maurer-Stroh S, Reading PC. Playing hide and seek: how glycosylation of the influenza virus hemagglutinin can modulate the immune response to infection. Viruses 2014; 6 (3) 1294-1316
    CrossrefPubMedGoogle Scholar
  • 71 Kim JI, Park MS. N-linked glycosylation in the hemagglutinin of influenza A viruses. Yonsei Med J 2012; 53 (5) 886-893
    CrossrefPubMedGoogle Scholar
  • 72 Vigerust DJ, Ulett KB, Boyd KL, Madsen J, Hawgood S, McCullers JA. N-linked glycosylation attenuates H3N2 influenza viruses. J Virol 2007; 81 (16) 8593-8600
    CrossrefPubMedGoogle Scholar
  • 73 Bautista E, Chotpitayasunondh T, Gao Z , et al; Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med 2010; 362 (18) 1708-1719
    CrossrefPubMedGoogle Scholar
  • 74 Short KR, Kroeze EJ, Fouchier RA, Kuiken T. Pathogenesis of influenza-induced acute respiratory distress syndrome. Lancet Infect Dis 2014; 14 (1) 57-69
    CrossrefPubMedGoogle Scholar
  • 75 Gack MU, Shin YC, Joo CH , et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 2007; 446 (7138) 916-920
    CrossrefPubMedGoogle Scholar
  • 76 Opitz B, Rejaibi A, Dauber B , et al. IFNbeta induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein. Cell Microbiol 2007; 9 (4) 930-938
    CrossrefPubMedGoogle Scholar
  • 77 Clemens MJ, Elia A. The double-stranded RNA-dependent protein kinase PKR: structure and function. J Interferon Cytokine Res 1997; 17 (9) 503-524
    CrossrefPubMedGoogle Scholar
  • 78 Gil J, Esteban M. Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): mechanism of action. Apoptosis 2000; 5 (2) 107-114
    CrossrefPubMedGoogle Scholar
  • 79 Kumar A, Haque J, Lacoste J, Hiscott J, Williams BR. Double-stranded RNA-dependent protein kinase activates transcription factor NF-kappa B by phosphorylating I kappa B. Proc Natl Acad Sci U S A 1994; 91 (14) 6288-6292
    CrossrefPubMedGoogle Scholar
  • 80 Perona-Wright G, Kohlmeier JE, Bassity E , et al. Persistent loss of IL-27 responsiveness in CD8+ memory T cells abrogates IL-10 expression in a recall response. Proc Natl Acad Sci U S A 2012; 109 (45) 18535-18540
    CrossrefPubMedGoogle Scholar
  • 81 Sun J, Dodd H, Moser EK, Sharma R, Braciale TJ. CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs. Nat Immunol 2011; 12 (4) 327-334
    CrossrefPubMedGoogle Scholar
  • 82 Sun J, Madan R, Karp CL, Braciale TJ. Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med 2009; 15 (3) 277-284
    CrossrefPubMedGoogle Scholar
  • 83 Ito Y, Torii Y, Ohta R , et al. Increased levels of cytokines and high-mobility group box 1 are associated with the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1 influenza-infected children. Cytokine 2011; 56 (2) 180-187
    CrossrefPubMedGoogle Scholar
  • 84 Tsai SY, Segovia JA, Chang TH , et al. DAMP molecule S100A9 acts as a molecular pattern to enhance inflammation during influenza A virus infection: role of DDX21-TRIF-TLR4-MyD88 pathway. PLoS Pathog 2014; 10 (1) e1003848
    CrossrefPubMedGoogle Scholar
  • 85 Kumagai Y, Takeuchi O, Kato H , et al. Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses. Immunity 2007; 27 (2) 240-252
    CrossrefPubMedGoogle Scholar
  • 86 Wang J, Nikrad MP, Travanty EA , et al. Innate immune response of human alveolar macrophages during influenza A infection. PLoS ONE 2012; 7 (3) e29879
    CrossrefPubMedGoogle Scholar
  • 87 Kim HM, Lee YW, Lee KJ , et al. Alveolar macrophages are indispensable for controlling influenza viruses in lungs of pigs. J Virol 2008; 82 (9) 4265-4274
    CrossrefPubMedGoogle Scholar
  • 88 Tumpey TM, García-Sastre A, Taubenberger JK , et al. Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice. J Virol 2005; 79 (23) 14933-14944
    CrossrefPubMedGoogle Scholar
  • 89 Imai Y, Kuba K, Neely GG , et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 2008; 133 (2) 235-249
    CrossrefPubMedGoogle Scholar
  • 90 Tate MD, Brooks AG, Reading PC. The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice. Respir Res 2008; 9: 57
    CrossrefPubMedGoogle Scholar
  • 91 Tate MD, Deng YM, Jones JE, Anderson GP, Brooks AG, Reading PC. Neutrophils ameliorate lung injury and the development of severe disease during influenza infection. J Immunol 2009; 183 (11) 7441-7450
    CrossrefPubMedGoogle Scholar
  • 92 Narasaraju T, Yang E, Samy RP , et al. Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol 2011; 179 (1) 199-210
    CrossrefPubMedGoogle Scholar
  • 93 Zemans RL, Colgan SP, Downey GP. Transepithelial migration of neutrophils: mechanisms and implications for acute lung injury. Am J Respir Cell Mol Biol 2009; 40 (5) 519-535
    CrossrefPubMedGoogle Scholar
  • 94 Saffarzadeh M, Juenemann C, Queisser MA , et al. Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PLoS ONE 2012; 7 (2) e32366
    CrossrefPubMedGoogle Scholar
  • 95 Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A. Neutrophil function: from mechanisms to disease. Annu Rev Immunol 2012; 30: 459-489
    CrossrefPubMedGoogle Scholar
  • 96 Brandes M, Klauschen F, Kuchen S, Germain RN. A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection. Cell 2013; 154 (1) 197-212
    CrossrefPubMedGoogle Scholar
  • 97 Ichikawa A, Kuba K, Morita M , et al. CXCL10-CXCR3 enhances the development of neutrophil-mediated fulminant lung injury of viral and nonviral origin. Am J Respir Crit Care Med 2013; 187 (1) 65-77
    CrossrefPubMedGoogle Scholar
  • 98 Tavian M, Péault B. Embryonic development of the human hematopoietic system. Int J Dev Biol 2005; 49 (2–3) 243-250
    CrossrefPubMedGoogle Scholar
  • 99 Fogg DK, Sibon C, Miled C , et al. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 2006; 311 (5757) 83-87
    CrossrefPubMedGoogle Scholar
  • 100 Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 2012; 122 (3) 787-795
    CrossrefPubMedGoogle Scholar
  • 101 Herold S, Mayer K, Lohmeyer J. Acute lung injury: how macrophages orchestrate resolution of inflammation and tissue repair. Front Immunol 2011; 2: 65
    PubMedGoogle Scholar
  • 102 Högner K, Wolff T, Pleschka S , et al. Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia. PLoS Pathog 2013; 9 (2) e1003188
    CrossrefPubMedGoogle Scholar
  • 103 Herold S, Steinmueller M, von Wulffen W , et al. Lung epithelial apoptosis in influenza virus pneumonia: the role of macrophage-expressed TNF-related apoptosis-inducing ligand. J Exp Med 2008; 205 (13) 3065-3077
    CrossrefPubMedGoogle Scholar
  • 104 Rodrigue-Gervais IG, Labbé K, Dagenais M , et al. Cellular inhibitor of apoptosis protein cIAP2 protects against pulmonary tissue necrosis during influenza virus infection to promote host survival. Cell Host Microbe 2014; 15 (1) 23-35
    CrossrefPubMedGoogle Scholar
  • 105 Davidson S, Crotta S, McCabe TM, Wack A. Pathogenic potential of interferon αβ in acute influenza infection. Nat Commun 2014; 5: 3864
    PubMedGoogle Scholar
  • 106 Peteranderl C, Morales-Nebreda L, Selvakumar B , et al. Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection. J Clin Invest 2016; 126 (4) 1566-1580
    CrossrefPubMedGoogle Scholar
  • 107 Unkel B, Hoegner K, Clausen BE , et al. Alveolar epithelial cells orchestrate DC function in murine viral pneumonia. J Clin Invest 2012; 122 (10) 3652-3664
    CrossrefPubMedGoogle Scholar
  • 108 Ichinohe T, Pang IK, Kumamoto Y , et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc Natl Acad Sci U S A 2011; 108 (13) 5354-5359
    CrossrefPubMedGoogle Scholar
  • 109 GeurtsvanKessel CH, Willart MA, van Rijt LS , et al. Clearance of influenza virus from the lung depends on migratory langerin+CD11b- but not plasmacytoid dendritic cells. J Exp Med 2008; 205 (7) 1621-1634
    CrossrefPubMedGoogle Scholar
  • 110 Soloff AC, Bissel SJ, Junecko BF , et al. Massive mobilization of dendritic cells during influenza A virus subtype H5N1 infection of nonhuman primates. J Infect Dis 2014; 209 (12) 2012-2016
    CrossrefPubMedGoogle Scholar
  • 111 Fernandez M, Miller E, Krammer F, Greenbaum B, Bhardwaj N. Ion efflux and influenza infection trigger NLRP3 inflammasome signaling in human dendritic cells. J Leukoc Biol 2016; 99 (5) 723-734
    CrossrefPubMedGoogle Scholar
  • 112 Ichinohe T, Lee HK, Ogura Y, Flavell R, Iwasaki A. Inflammasome recognition of influenza virus is essential for adaptive immune responses. J Exp Med 2009; 206 (1) 79-87
    CrossrefPubMedGoogle Scholar
  • 113 Hufford MM, Kim TS, Sun J, Braciale TJ. Antiviral CD8+ T cell effector activities in situ are regulated by target cell type. J Exp Med 2011; 208 (1) 167-180
    CrossrefPubMedGoogle Scholar
  • 114 Hufford MM, Richardson G, Zhou H , et al. Influenza-infected neutrophils within the infected lungs act as antigen presenting cells for anti-viral CD8(+) T cells. PLoS ONE 2012; 7 (10) e46581
    CrossrefPubMedGoogle Scholar
  • 115 McGill J, Van Rooijen N, Legge KL. Protective influenza-specific CD8 T cell responses require interactions with dendritic cells in the lungs. J Exp Med 2008; 205 (7) 1635-1646
    CrossrefPubMedGoogle Scholar
  • 116 Kim TS, Sun J, Braciale TJ. T cell responses during influenza infection: getting and keeping control. Trends Immunol 2011; 32 (5) 225-231
    CrossrefPubMedGoogle Scholar
  • 117 Teijaro JR, Walsh KB, Cahalan S , et al. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell 2011; 146 (6) 980-991
    CrossrefPubMedGoogle Scholar
  • 118 Zeng H, Pappas C, Belser JA , et al. Human pulmonary microvascular endothelial cells support productive replication of highly pathogenic avian influenza viruses: possible involvement in the pathogenesis of human H5N1 virus infection. J Virol 2012; 86 (2) 667-678
    CrossrefPubMedGoogle Scholar
  • 119 Ocaña-Macchi M, Bel M, Guzylack-Piriou L , et al. Hemagglutinin-dependent tropism of H5N1 avian influenza virus for human endothelial cells. J Virol 2009; 83 (24) 12947-12955
    CrossrefPubMedGoogle Scholar
  • 120 Ishiguro N, Takada A, Yoshioka M , et al. Induction of interferon-inducible protein-10 and monokine induced by interferon-gamma from human endothelial cells infected with Influenza A virus. Arch Virol 2004; 149 (1) 17-34
    PubMedGoogle Scholar
  • 121 Visseren FL, Verkerk MS, Bouter KP, Diepersloot RJ, Erkelens DW. Interleukin-6 production by endothelial cells after infection with influenza virus and cytomegalovirus. J Lab Clin Med 1999; 134 (6) 623-630
    CrossrefPubMedGoogle Scholar
  • 122 Huang F, Guo J, Zou Z , et al. Angiotensin II plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients. Nat Commun 2014; 5: 3595
    CrossrefPubMedGoogle Scholar
  • 123 Zou Z, Yan Y, Shu Y , et al. Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nat Commun 2014; 5: 3594
    CrossrefPubMedGoogle Scholar
  • 124 Teijaro JR, Walsh KB, Rice S, Rosen H, Oldstone MB. Mapping the innate signaling cascade essential for cytokine storm during influenza virus infection. Proc Natl Acad Sci U S A 2014; 111 (10) 3799-3804
    CrossrefPubMedGoogle Scholar
  • 125 Smith NM, Bresee JS, Shay DK, Uyeki TM, Cox NJ, Strikas RA ; Advisory Committee on Immunization Practices. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006; 55 (RR-10) 1-42
    PubMedGoogle Scholar
  • 126 WHO. WHO Guidelines for Pharmacological Management of Pandemic Influenza A (H1N1) and other Influenza Viruses. 2009. Available at: www.who.int/csr/resources/publications/swineflu/h1n1_guidelines_pharmaceutical_mngt.pdf
    PubMedGoogle Scholar
  • 127 People at High Risk of Developing Flu–Related Complications. 2015. Available at: http://www.cdc.gov/flu/about/disease/high_risk.htm . Accessed August 19, 2015
    PubMedGoogle Scholar
  • 128 Louie JK, Acosta M, Samuel MC , et al; California Pandemic (H1N1) Working Group. A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin Infect Dis 2011; 52 (3) 301-312
    CrossrefPubMedGoogle Scholar
  • 129 Louie JK, Acosta M, Winter K , et al; California Pandemic (H1N1) Working Group. Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. JAMA 2009; 302 (17) 1896-1902
    CrossrefPubMedGoogle Scholar
  • 130 Van Kerkhove MD, Vandemaele KA, Shinde V , et al; WHO Working Group for Risk Factors for Severe H1N1pdm Infection. Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis. PLoS Med 2011; 8 (7) e1001053
    CrossrefPubMedGoogle Scholar
  • 131 Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y. Avian flu: influenza virus receptors in the human airway. Nature 2006; 440 (7083) 435-436
    CrossrefPubMedGoogle Scholar
  • 132 van Riel D, den Bakker MA, Leijten LM , et al. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses. Am J Pathol 2010; 176 (4) 1614-1618
    CrossrefPubMedGoogle Scholar
  • 133 Mauad T, Hajjar LA, Callegari GD , et al. Lung pathology in fatal novel human influenza A (H1N1) infection. Am J Respir Crit Care Med 2010; 181 (1) 72-79
    CrossrefPubMedGoogle Scholar
  • 134 Rello J, Pop-Vicas A. Clinical review: primary influenza viral pneumonia. Crit Care 2009; 13 (6) 235
    CrossrefPubMedGoogle Scholar
  • 135 Rynda-Apple A, Robinson KM, Alcorn JF. Influenza and bacterial superinfection: illuminating the immunologic mechanisms of disease. Infect Immun 2015; 83 (10) 3764-3770
    CrossrefPubMedGoogle Scholar
  • 136 Blyth CC, Webb SA, Kok J , et al; ANZIC Influenza Investigators; COSI Microbiological Investigators. The impact of bacterial and viral co-infection in severe influenza. Influenza Other Respi Viruses 2013; 7 (2) 168-176
    CrossrefPubMedGoogle Scholar
  • 137 Goka E, Vallely P, Mutton K, Klapper P. Influenza A viruses dual and multiple infections with other respiratory viruses and risk of hospitalisation and mortality. Influenza Other Respi Viruses 2013; 7 (6) 1079-1087
    CrossrefPubMedGoogle Scholar
  • 138 Stefanska I, Romanowska M, Donevski S, Gawryluk D, Brydak LB. Co-infections with influenza and other respiratory viruses. Adv Exp Med Biol 2013; 756: 291-301
    PubMedGoogle Scholar
  • 139 Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet 2015; 385 (9979) 1729-1737
    CrossrefPubMedGoogle Scholar
  • 140 Storms AD, Gubareva LV, Su S , et al; US Antiviral Resistance Surveillance Working Group. Oseltamivir-resistant pandemic (H1N1) 2009 virus infections, United States, 2010-11. Emerg Infect Dis 2012; 18 (2) 308-311
    CrossrefPubMedGoogle Scholar
  • 141 Dunning J, Baillie JK, Cao B, Hayden FG ; International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). Antiviral combinations for severe influenza. Lancet Infect Dis 2014; 14 (12) 1259-1270
    CrossrefPubMedGoogle Scholar
  • 142 Louie JK, Yang S, Acosta M , et al. Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09. Clin Infect Dis 2012; 55 (9) 1198-1204
    CrossrefPubMedGoogle Scholar
  • 143 Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S , et al; INER Working Group on Influenza. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med 2009; 361 (7) 680-689
    CrossrefPubMedGoogle Scholar
  • 144 Napolitano LM, Park PK, Raghavendran K, Bartlett RH. Nonventilatory strategies for patients with life-threatening 2009 H1N1 influenza and severe respiratory failure. Crit Care Med 2010; 38 (4, Suppl): e74-e90
    CrossrefPubMedGoogle Scholar
  • 145 Estenssoro E, Ríos FG, Apezteguía C , et al; Registry of the Argentinian Society of Intensive Care SATI. Pandemic 2009 influenza A in Argentina: a study of 337 patients on mechanical ventilation. Am J Respir Crit Care Med 2010; 182 (1) 41-48
    CrossrefPubMedGoogle Scholar
  • 146 Ventetuolo CE, Muratore CS. Extracorporeal life support in critically ill adults. Am J Respir Crit Care Med 2014; 190 (5) 497-508
    CrossrefPubMedGoogle Scholar
  • 147 Kim SH, Hong SB, Yun SC , et al; Korean Society of Critical Care Medicine H1N1 Collaborative. Corticosteroid treatment in critically ill patients with pandemic influenza A/H1N1 2009 infection: analytic strategy using propensity scores. Am J Respir Crit Care Med 2011; 183 (9) 1207-1214
    CrossrefPubMedGoogle Scholar
  • 148 Hui DS, Lee N, Chan PK. Clinical management of pandemic 2009 influenza A(H1N1) infection. Chest 2010; 137 (4) 916-925
    CrossrefPubMedGoogle Scholar
  • 149 Jain S, Benoit SR, Skarbinski J, Bramley AM, Finelli L ; 2009 Pandemic Influenza A (H1N1) Virus Hospitalizations Investigation Team. Influenza-associated pneumonia among hospitalized patients with 2009 pandemic influenza A (H1N1) virus—United States, 2009. Clin Infect Dis 2012; 54 (9) 1221-1229
    Google Scholar
  • 150 Morens DM, Taubenberger JK, Harvey HA, Memoli MJ. The 1918 influenza pandemic: lessons for 2009 and the future. Crit Care Med 2010; 38 (4, Suppl): e10-e20
    CrossrefPubMedGoogle Scholar
  • 151 Cortes Garcia M, Sierra Moros MJ, Santa-Olalla Peralta P, Hernandez-Barrera V, Jimenez-Garcia R, Pachon I. Clinical characteristics and outcomes of diabetic patients who were hospitalised with 2009 pandemic influenza A H1N1 infection. J Infect 2012; 64 (2) 218-224
    CrossrefPubMedGoogle Scholar
  • 152 Rodríguez-Rieiro C, Carrasco-Garrido P, Hernández-Barrera V , et al. Pandemic influenza hospitalization in Spain (2009): incidence, in-hospital mortality, comorbidities and costs. Hum Vaccin Immunother 2012; 8 (4) 443-447
    CrossrefPubMedGoogle Scholar
  • 153 CDC. People at High Risk of Developing Flu–Related Complications; 2015. Available at: http://www.cdc.gov/flu/about/disease/high_risk.htm . Accessed July 17, 2015
    PubMedGoogle Scholar
  • 154 Memoli MJ, Athota R, Reed S , et al. The natural history of influenza infection in the severely immunocompromised vs nonimmunocompromised hosts. Clin Infect Dis 2014; 58 (2) 214-224
    CrossrefPubMedGoogle Scholar
  • 155 Camargo LF, de Sandes-Freitas TV, Silva CD , et al. Morbimortality of pandemic influenza A H1N1 infection in kidney transplant recipients requiring hospitalization: a comparative analysis with nonimmunocompromised patients. Transplantation 2012; 93 (1) 69-72
    CrossrefPubMedGoogle Scholar
  • 156 ANZIC Influenza Investigators and Australasian Maternity Outcomes Surveillance System. Critical illness due to 2009 A/H1N1 influenza in pregnant and postpartum women: population based cohort study. BMJ 2010; 340: c1279
    CrossrefPubMedGoogle Scholar
  • 157 Mosby LG, Rasmussen SA, Jamieson DJ. 2009 pandemic influenza A (H1N1) in pregnancy: a systematic review of the literature. Am J Obstet Gynecol 2011; 205 (1) 10-18
    CrossrefPubMedGoogle Scholar
  • 158 World Health Organization. Pregnancy and Pandemic Influenza A (H1N1) 2009: Information for Programme Managers and Clinicians; 2010. Available at: http://www.who.int/csr/resources/publications/swineflu/h1n1_guidance_pregnancy.pdf?ua=1 . Accessed July 20, 2015
    PubMedGoogle Scholar
  • 159 Centers for Disease Control and Prevention (CDC). Maternal and infant outcomes among severely ill pregnant and postpartum women with 2009 pandemic influenza A (H1N1)—United States, April 2009-August 2010. MMWR Morb Mortal Wkly Rep 2011; 60 (35) 1193-1196
    PubMedGoogle Scholar
  • 160 Forbes RL, Wark PA, Murphy VE, Gibson PG. Pregnant women have attenuated innate interferon responses to 2009 pandemic influenza A virus subtype H1N1. J Infect Dis 2012; 206 (5) 646-653
    CrossrefPubMedGoogle Scholar
  • 161 Acs N, Bánhidy F, Puhó E, Czeizel AE. Maternal influenza during pregnancy and risk of congenital abnormalities in offspring. Birth Defects Res A Clin Mol Teratol 2005; 73 (12) 989-996
    CrossrefPubMedGoogle Scholar
  • 162 Seasonal influenza vaccination in Europe—Vaccination recommendations and coverage rates, 2012–2013. Available at: http://ecdc.europa.eu/en/healthtopics/seasonal_influenza/vaccines/Pages/vaccines.aspx . Accessed October 16, 2015
    PubMedGoogle Scholar
  • 163 Albright FS, Orlando P, Pavia AT, Jackson GG, Cannon Albright LA. Evidence for a heritable predisposition to death due to influenza. J Infect Dis 2008; 197 (1) 18-24
    CrossrefPubMedGoogle Scholar
  • 164 Everitt AR, Clare S, Pertel T , et al; GenISIS Investigators; MOSAIC Investigators. IFITM3 restricts the morbidity and mortality associated with influenza. Nature 2012; 484 (7395) 519-523
    CrossrefPubMedGoogle Scholar
  • 165 Wang Z, Zhang A, Wan Y , et al. Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection. Proc Natl Acad Sci U S A 2014; 111 (2) 769-774
    CrossrefPubMedGoogle Scholar
  • 166 Mills TC, Rautanen A, Elliott KS , et al. IFITM3 and susceptibility to respiratory viral infections in the community. J Infect Dis 2014; 209 (7) 1028-1031
    CrossrefPubMedGoogle Scholar
  • 167 Williams DE, Wu WL, Grotefend CR , et al. IFITM3 polymorphism rs12252-C restricts influenza A viruses. PLoS ONE 2014; 9 (10) e110096
    CrossrefPubMedGoogle Scholar
  • 168 Ciancanelli MJ, Huang SX, Luthra P , et al. Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science 2015; 348 (6233) 448-453
    CrossrefPubMedGoogle Scholar
  • 169 Liu Y, Li S, Zhang G , et al. Genetic variants in IL1A and IL1B contribute to the susceptibility to 2009 pandemic H1N1 influenza A virus. BMC Immunol 2013; 14: 37
    CrossrefPubMedGoogle Scholar
  • 170 Cheng Z, Zhou J, To KK , et al. Identification of TMPRSS2 as a Susceptibility Gene for Severe 2009 Pandemic A(H1N1) Influenza and A(H7N9) Influenza. J Infect Dis 2015; 212 (8) 1214-1221
    CrossrefPubMedGoogle Scholar
  • 171 Chen Y, Zhou J, Cheng Z , et al. Functional variants regulating LGALS1 (Galectin 1) expression affect human susceptibility to influenza A(H7N9). Sci Rep 2015; 5: 8517
    CrossrefPubMedGoogle Scholar
  • 172 Reed C, Kim IK, Singleton JA , et al; Centers for Disease Control and Prevention (CDC). Estimated influenza illnesses and hospitalizations averted by vaccination—United States, 2013-14 influenza season. MMWR Morb Mortal Wkly Rep 2014; 63 (49) 1151-1154
    PubMedGoogle Scholar
  • 173 Grohskopf LA, Sokolow LZ, Olsen SJ, Bresee JS, Broder KR, Karron RA. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 Influenza Season. MMWR Morb Mortal Wkly Rep 2015; 64 (30) 818-825
    CrossrefPubMedGoogle Scholar
  • 174 Lukashevich IS, Shirwan H , eds. Novel Technologies for Vaccine Development. Vienna: Springer; 2014
    CrossrefGoogle Scholar
  • 175 Clements ML, Murphy BR. Development and persistence of local and systemic antibody responses in adults given live attenuated or inactivated influenza A virus vaccine. J Clin Microbiol 1986; 23 (1) 66-72
    PubMedGoogle Scholar
  • 176 Nunes-Alves C. Viral infection: stemming influenza viruses. Nat Rev Microbiol 2015; 13 (10) 599
    CrossrefPubMedGoogle Scholar
  • 177 Impagliazzo A, Milder F, Kuipers H , et al. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science 2015; 349 (6254) 1301-1306
    CrossrefPubMedGoogle Scholar
  • 178 Dempsey LA. Universal influenza vaccine. Nat Immunol 2015; 16: 1013
    PubMedGoogle Scholar
  • 179 Maassab HF. Biologic and immunologic characteristics of cold-adapted influenza virus. J Immunol 1969; 102 (3) 728-732
    PubMedGoogle Scholar
  • 180 Beyer WE, Palache AM, de Jong JC, Osterhaus AD. Cold-adapted live influenza vaccine verss inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis. Vaccine 2002; 20 (9–10) 1340-1353
    CrossrefPubMedGoogle Scholar
  • 181 Fleury D, Barrère B, Bizebard T, Daniels RS, Skehel JJ, Knossow M. A complex of influenza hemagglutinin with a neutralizing antibody that binds outside the virus receptor binding site. Nat Struct Biol 1999; 6 (6) 530-534
    CrossrefPubMedGoogle Scholar
  • 182 Wei G, Meng W, Guo H , et al. Potent neutralization of influenza A virus by a single-domain antibody blocking M2 ion channel protein. PLoS ONE 2011; 6 (12) e28309
    CrossrefPubMedGoogle Scholar
  • 183 Smee DF, Bailey KW, Wong MH , et al. Treatment of influenza A (H1N1) virus infections in mice and ferrets with cyanovirin-N. Antiviral Res 2008; 80 (3) 266-271
    CrossrefPubMedGoogle Scholar
  • 184 Furuta Y, Takahashi K, Shiraki K , et al. T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections. Antiviral Res 2009; 82 (3) 95-102
    CrossrefPubMedGoogle Scholar
  • 185 Furuta Y, Takahashi K, Fukuda Y , et al. In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob Agents Chemother 2002; 46 (4) 977-981
    CrossrefPubMedGoogle Scholar
  • 186 Sidwell RW, Smee DF. Peramivir (BCX-1812, RWJ-270201): potential new therapy for influenza. Expert Opin Investig Drugs 2002; 11 (6) 859-869
    CrossrefPubMedGoogle Scholar
  • 187 Weight AK, Haldar J, Alvarez de Cienfuegos L , et al. Attaching zanamivir to a polymer markedly enhances its activity against drug-resistant strains of influenza a virus. J Pharm Sci 2011; 100 (3) 831-835
    CrossrefPubMedGoogle Scholar
  • 188 Mitrasinovic PM. Advances in the structure-based design of the influenza A neuraminidase inhibitors. Curr Drug Targets 2010; 11 (3) 315-326
    CrossrefPubMedGoogle Scholar
  • 189 Lin L, Liu Q, Berube N, Detmer S, Zhou Y. 5′-Triphosphate-short interfering RNA: potent inhibition of influenza A virus infection by gene silencing and RIG-I activation. J Virol 2012; 86 (19) 10359-10369
    CrossrefPubMedGoogle Scholar
  • 190 Tompkins SM, Lo CY, Tumpey TM, Epstein SL. Protection against lethal influenza virus challenge by RNA interference in vivo. Proc Natl Acad Sci U S A 2004; 101 (23) 8682-8686
    CrossrefPubMedGoogle Scholar
  • 191 Loregian A, Mercorelli B, Nannetti G, Compagnin C, Palù G. Antiviral strategies against influenza virus: towards new therapeutic approaches. Cell Mol Life Sci 2014; 71 (19) 3659-3683
    CrossrefPubMedGoogle Scholar
  • 192 Malakhov MP, Aschenbrenner LM, Smee DF , et al. Sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus infection. Antimicrob Agents Chemother 2006; 50 (4) 1470-1479
    CrossrefPubMedGoogle Scholar
  • 193 Triana-Baltzer GB, Sanders RL, Hedlund M , et al. Phenotypic and genotypic characterization of influenza virus mutants selected with the sialidase fusion protein DAS181. J Antimicrob Chemother 2011; 66 (1) 15-28
    CrossrefPubMedGoogle Scholar
  • 194 Triana-Baltzer GB, Gubareva LV, Klimov AI , et al. Inhibition of neuraminidase inhibitor-resistant influenza virus by DAS181, a novel sialidase fusion protein. PLoS ONE 2009; 4 (11) e7838
    CrossrefPubMedGoogle Scholar
  • 195 Kido H, Okumura Y, Yamada H, Le TQ, Yano M. Proteases essential for human influenza virus entry into cells and their inhibitors as potential therapeutic agents. Curr Pharm Des 2007; 13 (4) 405-414
    CrossrefPubMedGoogle Scholar
  • 196 Ludwig S, Zell R, Schwemmle M, Herold S. Influenza, a One Health paradigm—novel therapeutic strategies to fight a zoonotic pathogen with pandemic potential. Int J Med Microbiol 2014; 304 (7) 894-901
    CrossrefPubMedGoogle Scholar
  • 197 Register ECT . Available at: https://wwwclinicaltrialsregistereu/ctr-search/trial/2012-004072-19/DE
    PubMed
  • 198 Wang X, Hinson ER, Cresswell P. The interferon-inducible protein viperin inhibits influenza virus release by perturbing lipid rafts. Cell Host Microbe 2007; 2 (2) 96-105
    CrossrefPubMedGoogle Scholar
  • 199 Morita M, Kuba K, Ichikawa A , et al. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell 2013; 153 (1) 112-125
    CrossrefPubMedGoogle Scholar
  • 200 Aver'ianov AV, Babkin AP, Bart BIa , et al. Ergoferon and oseltamivir in treatment of influenza: results of multicentre randomized comparative clinical trial [in Russian]. Antibiot Khimioter 2012; 57 (7–8) 23-30
    PubMedGoogle Scholar
  • 201 Sever-Chroneos Z, Murthy A, Davis J , et al. GM-CSF modulates pulmonary resistance to influenza A infection. Antiviral Res 2011; 92 (2) 319-328
    CrossrefPubMedGoogle Scholar
  • 202 Cakarova L, Marsh LM, Wilhelm J , et al. Macrophage tumor necrosis factor-alpha induces epithelial expression of granulocyte-macrophage colony-stimulating factor: impact on alveolar epithelial repair. Am J Respir Crit Care Med 2009; 180 (6) 521-532
    CrossrefPubMedGoogle Scholar
  • 203 Huang FF, Barnes PF, Feng Y , et al. GM-CSF in the lung protects against lethal influenza infection. Am J Respir Crit Care Med 2011; 184 (2) 259-268
    CrossrefPubMedGoogle Scholar
  • 204 Herold S, Hoegner K, Vadász I , et al. Inhaled granulocyte/macrophage colony-stimulating factor as treatment of pneumonia-associated acute respiratory distress syndrome. Am J Respir Crit Care Med 2014; 189 (5) 609-611
    CrossrefPubMedGoogle Scholar
  • 205 Ho MS, Mei SH, Stewart DJ. The immunomodulatory and therapeutic effects of mesenchymal stromal cells for acute lung injury and sepsis. J Cell Physiol 2015; 230 (11) 2606-2617
    CrossrefPubMedGoogle Scholar
  • 206 Lalu MM, Moher D, Marshall J , et al; Canadian Critical Care Translational Biology Group. Efficacy and safety of mesenchymal stromal cells in preclinical models of acute lung injury: a systematic review protocol. Syst Rev 2014; 3: 48
    CrossrefPubMedGoogle Scholar
  • 207 Wilson JG, Liu KD, Zhuo H , et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med 2015; 3 (1) 24-32
    CrossrefPubMedGoogle Scholar
  • 208 Weiss DJ. Cell therapies for ARDS: a promising start. Lancet Respir Med 2015; 3 (1) 2-3
    CrossrefPubMedGoogle Scholar
  • 209 Leeman KT, Fillmore CM, Kim CF. Lung stem and progenitor cells in tissue homeostasis and disease. Curr Top Dev Biol 2014; 107: 207-233
    PubMedGoogle Scholar
  • 210 Vaughan AE, Brumwell AN, Xi Y , et al. Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Nature 2015; 517 (7536) 621-625
    PubMedGoogle Scholar
  • 211 Quantius J, Schmoldt C, Vazquez-Armendariz I , et al. Influenza Virus infects epithelial stem/progenitor cells of the distal lung: impact on Fgfr2b-driven epithelial repair. PLOS Pathog 2016; ; in press
    PubMedGoogle Scholar