1.Sellers, S. A., Hagan, R. S., Hayden, F. G. & Fischer, W. A. 2nd. The hidden burden of influenza: A evaluation of the extra-pulmonary issues of influenza an infection. Influenza Different Respir. Viruses 11, 372–393 (2017).2.Kwong, J. C. et al. Acute myocardial infarction after laboratory-confirmed influenza an infection. N. Engl. J. Med. 378, 345–353 (2018).three.Matsuzaki, Y. et al. Scientific options of influenza C virus an infection in kids. J. Infect. Dis. 193, 1229–1235 (2006).four.Olsen, B. et al. World patterns of influenza a virus in wild birds. Science 312, 384–388 (2006).5.Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M. & Kawaoka, Y. Evolution and ecology of influenza A viruses. Microbiol. Rev. 56, 152–179 (1992).6.Tong, S. et al. A definite lineage of influenza A virus from bats. Proc. Natl Acad. Sci. USA 109, 4269–4274 (2012).7.Ma, W., García-Sastre, A. & Schwemmle, M. Anticipated and surprising options of the newly found bat influenza A-like viruses. PLOS Pathog. 11, e1004819 (2015).eight.Fouchier, R. A. et al. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J. Virol. 79, 2814–2822 (2005).9.Osterhaus, A. D., Rimmelzwaan, G. F., Martina, B. E., Bestebroer, T. M. & Fouchier, R. A. Influenza B virus in seals. Science 288, 1051–1053 (2000).10.Guo, Y. J., Jin, F. G., Wang, P., Wang, M. & Zhu, J. M. Isolation of influenza C virus from pigs and experimental an infection of pigs with influenza C virus. J. Gen. Virol. 64, 177–182 (1983).11.Hause, B. M. et al. Isolation of a novel swine influenza virus from Oklahoma in 2011 which is distantly associated to human influenza C viruses. PLOS Pathog. 9, e1003176 (2013).12.Hause, B. M. et al. Characterization of a novel influenza virus in cattle and Swine: proposal for a brand new genus within the Orthomyxoviridae household. MBio 5, e00031–00014 (2014).13.Smith, G. J. et al. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 459, 1122–1125 (2009).14.Mena, I. et al. Origins of the 2009 H1N1 influenza pandemic in swine in Mexico. elife 5, e.16777 (2016). This reference tracks the origins of a human pandemic influenza A virus for the primary time.15.Hayden, F. Growing new antiviral brokers for influenza remedy: what does the longer term maintain? Clin. Infect. Dis. 48 (Suppl. 1), S3–S13 (2009).16.Damage, A. C. et al. Antiviral resistance in the course of the 2009 influenza A H1N1 pandemic: public well being, laboratory, and scientific views. Lancet Infect. Dis. 12, 240–248 (2012).17.Rambaut, A. et al. The genomic and epidemiological dynamics of human influenza A virus. Nature 453, 615–619 (2008).18.Russell, C. A. et al. The worldwide circulation of seasonal influenza A (H3N2) viruses. Science 320, 340–346 (2008). Along with reference 17, this seminal examine proposes intriguing fashions of how influenza viruses are maintained within the human inhabitants and transmitted globally throughout seasonal epidemics.19.Bahl, J. et al. Temporally structured metapopulation dynamics and persistence of influenza A H3N2 virus in people. Proc. Natl Acad. Sci. USA 108, 19359–19364 (2011).20.Yu, H. et al. Characterization of regional influenza seasonality patterns in China and implications for vaccination methods: spatio-temporal modeling of surveillance information. PLOS Med. 10, e1001552 (2013).21.Facilities for Illness Management and Prevention. Estimated influenza sicknesses and hospitalizations averted by vaccination — United States, 2014–15 influenza season. CDC (2015).22.Cohen, S. A., Chui, Ok. Ok. & Naumova, E. N. Influenza vaccination in younger kids reduces influenza-associated hospitalizations in older adults, 2002–2006. J. Am. Geriatr. Soc. 59, 327–332 (2011).23.Gostic, Ok. M., Ambrose, M., Worobey, M. & Lloyd-Smith, J. O. Potent safety in opposition to H5N1 and H7N9 influenza through childhood hemagglutinin imprinting. Science 354, 722–726 (2016).24.Lozano, R. et al. World and regional mortality from 235 causes of demise for 20 age teams in 1990 and 2010: a scientific evaluation for the World Burden of Illness Research 2010. Lancet 380, 2095–2128 (2012).25.Iuliano, A. D. et al. Estimates of worldwide seasonal influenza-associated respiratory mortality: a modelling examine. Lancet 391, 1285–1300 (2018).26.Thompson, W. W. et al. Mortality related to influenza and respiratory syncytial virus in america. JAMA 289, 179–186 (2003).This examine represents a basic evaluation of hospital-acquired pneumonia and influenza deaths that establishes the influence of seasonal influenza in america.27.Flannery, B. et al. Influenza vaccine effectiveness in opposition to pediatric deaths: 2010–2014. Pediatrics 139, (2017).28.Thompson, W. W. et al. Influenza-associated hospitalizations in america. JAMA 292, 1333–1340 (2004).29.Walsh, E. E., Cox, C. & Falsey, A. R. Scientific options of influenza A virus an infection in older hospitalized individuals. J. Am. Geriatr. Soc. 50, 1498–1503 (2002).30.Jain, S. et al. Hospitalized sufferers with 2009 H1N1 influenza in america, April-June 2009. N. Engl. J. Med. 361, 1935–1944 (2009).31.Keren, R. et al. Neurological and neuromuscular illness as a threat issue for respiratory failure in kids hospitalized with influenza an infection. JAMA 294, 2188–2194 (2005).32.Neuzil, Ok. M., Reed, G. W., Mitchel, E. F., Simonsen, L. & Griffin, M. R. Impression of influenza on acute cardiopulmonary hospitalizations in pregnant girls. Am. J. Epidemiol. 148, 1094–1102 (1998).33.Van Kerkhove, M. D. et al. Danger elements for extreme outcomes following 2009 influenza A (H1N1) an infection: a world pooled evaluation. PLOS Med. eight, e1001053 (2011).34.Karlsson, E. A. et al. An ideal storm: Elevated colonization and failure of vaccination results in extreme secondary bacterial an infection in influenza virus-infected overweight mice. MBio eight, e00889-17 (2017).35.Ciancanelli, M. J. et al. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science 348, 448–453 (2015).36.Everitt, A. R. et al. IFITM3 restricts the morbidity and mortality related to influenza. Nature 484, 519–523 (2012).37.Allen, E. Ok. et al. SNP-mediated disruption of CTCF binding on the IFITM3 promoter is related to threat of extreme influenza in people. Nat. Med. 23, 975–983 (2017).38.van Gils, J. A. et al. Hampered foraging and migratory efficiency in swans contaminated with low-pathogenic avian influenza A virus. PLOS ONE 2, e184 (2007).39.Guan, Y. & Smith, G. J. The emergence and diversification of panzootic H5N1 influenza viruses. Virus Res. 178, 35–43 (2013).40.Ip, H. S. et al. Novel Eurasian extremely pathogenic avian influenza A H5 viruses in wild birds, WA, USA, 2014. Emerg. Infect. Dis. 21, 886–890 (2015).41.Ke, C. et al. Human an infection with extremely pathogenic avian influenza A(H7N9) virus. China. Emerg. Infect. Dis. 23, 1332–1340 (2017).42.Lee, C. T. et al. Outbreak of influenza A(H7N2) amongst cats in an animal shelter with cat-to-human transmission-New York Metropolis, 2016. Clin. Infect. Dis. 65, 1927–1929 (2017).43.Fouchier, R. A. et al. Avian influenza A virus (H7N7) related to human conjunctivitis and a deadly case of acute respiratory misery syndrome. Proc. Natl Acad. Sci. USA 101, 1356–1361 (2004).44.Perkins, L. E. & Swayne, D. E. Pathogenicity of a Hong Kong-origin H5N1 extremely pathogenic avian influenza virus for emus, geese, geese, and pigeons. Avian Dis. 46, 53–63 (2002).45.Hulse-Submit, D. J. et al. Function of home geese within the propagation and organic evolution of extremely pathogenic H5N1 influenza viruses in Asia. Proc. Natl Acad. Sci. USA 102, 10682–10687 (2005).46.Fournie, G. et al. Interventions for avian influenza A (H5N1) threat administration in stay hen market networks. Proc. Natl Acad. Sci. USA 110, 9177–9182 (2013).47.Vincent, A. et al. Evaluation of influenza A virus in swine worldwide: a name for elevated surveillance and analysis. Zoonoses Publ. Well being 61, four–17 (2014).48.Neumann, G. & Kawaoka, Y. The primary influenza pandemic of the brand new millennium. Influenza Different Respir. Viruses 5, 157–166 (2011).49.Jhung, M. A. et al. Outbreak of variant influenza A(H3N2) virus in america. Clin. Infect. Dis. 57, 1703–1712 (2013).50.Crawford, P. C. et al. Transmission of equine influenza virus to canines. Science 310, 482–485 (2005).51.Li, S. et al. Avian-origin H3N2 canine influenza A viruses in Southern China. Infect. Genet. Evol. 10, 1286–1288 (2010).52.Yamada, S. et al. Haemagglutinin mutations answerable for the binding of H5N1 influenza A viruses to human-type receptors. Nature 444, 378–382 (2006).53.van Riel, D. et al. H5N1 virus attachment to decrease respiratory tract. Science 312, 399 (2006).54.Hirst, G. Ok. Research of antigenic variations amongst strains of influenza A by way of pink cell agglutination. J. Exp. Med. 78, 407–423 (1943).55.Barr, I. G. et al. WHO suggestions for the viruses used within the 2013–2014 Northern Hemisphere influenza vaccine: epidemiology, antigenic and genetic traits of influenza A(H1N1)pdm09, A(H3N2) and B influenza viruses collected from October 2012 to January 2013. Vaccine 32, 4713–4725 (2014).56.Sandbulte, M. R. et al. Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses. Proc. Natl Acad. Sci. USA 108, 20748–20753 (2011).57.Kilbourne, E. D., Laver, W. G., Schulman, J. L. & Webster, R. G. Antiviral exercise of antiserum particular for an influenza virus neuraminidase. J. Virol. 2, 281–288 (1968).58.Couzens, L. et al. An optimized enzyme-linked lectin assay to measure influenza A virus neuraminidase inhibition antibody titers in human sera. J. Virol. Strategies 210, 7–14 (2014).59.Voeten, J. T. et al. Antigenic drift within the influenza A virus (H3N2) nucleoprotein and escape from recognition by cytotoxic T lymphocytes. J. Virol. 74, 6800–6807 (2000).60.Smith, D. J. et al. Mapping the antigenic and genetic evolution of influenza virus. Science 305, 371–376 (2004).This examine describes the idea of antigenic cartography and makes use of antigenic cartography for the visualization and quantification of antigenic drift of human H3N2 influenza A viruses over 35 years.61.Koel, B. F. et al. Substitutions close to the receptor binding web site decide main antigenic change throughout influenza virus evolution. Science 342, 976–979 (2013).62.Koel, B. F. et al. Antigenic variation of clade 2.1 H5N1 virus is decided by a couple of amino acid substitutions instantly adjoining to the receptor binding web site. MBio 5, e01070-01014 (2014).63.Lewis, N. S. et al. Antigenic and genetic evolution of equine influenza A (H3N8) virus from 1968 to 2007. J. Virol. 85, 12742–12749 (2011) Jong, J. C. et al. Antigenic and genetic evolution of swine influenza A (H3N2) viruses in Europe. J. Virol. 81, 4315–4322 (2007).65.Kendal, A. P., Noble, G. R., Skehel, J. J. & Dowdle, W. R. Antigenic similarity of influenza A (H1N1) viruses from epidemics in 1977—1978 to “Scandinavian” strains remoted in epidemics of 1950–1951. Virology 89, 632–636 (1978).66.Herfst, S. et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science 336, 1534–1541 (2012).67.Imai, M. et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 486, 420–428 (2012).68.Russell, C. A. et al. The potential for respiratory droplet-transmissible A/H5N1 influenza virus to evolve in a mammalian host. Science 336, 1541–1547 (2012).69.Yoon, S. W., Webby, R. J. & Webster, R. G. Evolution and ecology of influenza A viruses. Curr. High. Microbiol. Immunol. 385, 359–375 (2014).70.Webster, R. G. & Hulse, D. J. Microbial adaptation and alter: avian influenza. Rev. Sci. Tech. 23, 453–465 (2004).71.Andino, R. & Domingo, E. Viral quasispecies. Virology 479–480, 46–51 (2015).72.Tumpey, T. M. et al. A two-amino acid change within the hemagglutinin of the 1918 influenza virus abolishes transmission. Science 315, 655–659 (2007). This examine supplies the primary proof that the receptor specificity of the HA of influenza A virus performs a serious function within the respiratory transmission of those viruses.73.Mitnaul, L. J. et al. Balanced hemagglutinin and neuraminidase actions are important for environment friendly replication of influenza A virus. J. Virol. 74, 6015–6020 (2000).74.Reed, M. L. et al. The pH of activation of the hemagglutinin protein regulates H5N1 influenza virus pathogenicity and transmissibility in geese. J. Virol. 84, 1527–1535 (2010).75.Hatta, M., Gao, P., Halfmann, P. & Kawaoka, Y. Molecular foundation for prime virulence of Hong Kong H5N1 influenza A viruses. Science 293, 1840–1842 (2001).76.Mehle, A. & Doudna, J. A. Adaptive methods of the influenza virus polymerase for replication in people. Proc. Natl Acad. Sci. USA 106, 21312–21316 (2009).77.Riegger, D. et al. The nucleoprotein of newly emerged H7N9 influenza A virus harbors a singular motif conferring resistance to antiviral human MxA. J. Virol. 89, 2241–2252 (2015).78.Campbell, P. J. et al. The M phase of the 2009 pandemic influenza virus confers elevated neuraminidase exercise, filamentous morphology, and environment friendly contact transmissibility to A/Puerto Rico/eight/1934-based reassortant viruses. J. Virol. 88, 3802–3814 (2014).79.Medina, R. A. & García-Sastre, A. Influenza A viruses: new analysis developments. Nat. Rev. Microbiol. 9, 590–603 (2011).80.Tong, S. et al. New world bats harbor numerous influenza A viruses. PLOS Pathog. 9, e1003657 (2013).81.Moreira, E. A. et al. Synthetically derived bat influenza A-like viruses reveal a cell type- however not species-specific tropism. Proc. Natl Acad. Sci. USA 113, 12797–12802 (2016).82.Mibayashi, M. et al. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. J. Virol. 81, 514–524 (2007).83.Pichlmair, A. et al. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 314, 997–1001 (2006).84.Rajsbaum, R. et al. Species-specific inhibition of RIG-I ubiquitination and IFN induction by the influenza A virus NS1 protein. PLOS Pathog. eight, e1003059 (2012).85.Nemeroff, M. E., Barabino, S. M., Li, Y., Keller, W. & Krug, R. M. Influenza virus NS1 protein interacts with the mobile 30 kDa subunit of CPSF and inhibits three′finish formation of mobile pre-mRNAs. Mol. Cell 1, 991–1000 (1998).86.Satterly, N. et al. Influenza virus targets the mRNA export equipment and the nuclear pore complicated. Proc. Natl Acad. Sci. USA 104, 1853–1858 (2007).87.Marazzi, I. et al. Suppression of the antiviral response by an influenza histone mimic. Nature 483, 428–433 (2012).88.Chauche, C. et al. Mammalian adaptation of an avian influenza A virus entails stepwise adjustments in NS1. J. Virol. e01875-17 (2017).89.Li, S., Min, J. Y., Krug, R. M. & Sen, G. C. Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by both PACT or double-stranded RNA. Virology 349, 13–21 (2006).90.Min, J. Y. & Krug, R. M. The first operate of RNA binding by the influenza A virus NS1 protein in contaminated cells: Inhibiting the two′-5′ oligo (A) synthetase/RNase L pathway. Proc. Natl Acad. Sci. USA 103, 7100–7105 (2006).91.Conenello, G. M. & Palese, P. Influenza A virus PB1-F2: a small protein with an enormous punch. Cell Host Microbe 2, 207–209 (2007).92.Graef, Ok. M. et al. The PB2 subunit of the influenza virus RNA polymerase impacts virulence by interacting with the mitochondrial antiviral signaling protein and inhibiting expression of beta interferon. J. Virol. 84, 8433–8445 (2010).93.Jagger, B. W. et al. An overlapping protein-coding area in influenza A virus phase three modulates the host response. Science 337, 199–204 (2012).94.Crotta, S. et al. Sort I and kind III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia. PLOS Pathog. 9, e1003773 (2013).95.Helft, J. et al. Cross-presenting CD103+ dendritic cells are protected against influenza virus an infection. J. Clin. Make investments. 122, 4037–4047 (2012).96.Zhu, L. et al. Excessive degree of neutrophil extracellular traps correlates with poor prognosis of extreme influenza A an infection. J. Infect. Dis. 217, 428–437 (2018).97.Walsh, Ok. B. et al. Suppression of cytokine storm with a sphingosine analog supplies safety in opposition to pathogenic influenza virus. Proc. Natl Acad. Sci. USA 108, 12018–12023 (2011).98.Sridhar, S. et al. Mobile immune correlates of safety in opposition to symptomatic pandemic influenza. Nat. Med. 19, 1305–1312 (2013).99.Wilkinson, T. M. et al. Preexisting influenza-specific CD4+ T cells correlate with illness safety in opposition to influenza problem in people. Nat. Med. 18, 274–280 (2012).100.Quinones-Parra, S. et al. Preexisting CD8+ T cell immunity to the H7N9 influenza A virus varies throughout ethnicities. Proc. Natl Acad. Sci. USA 111, 1049–1054 (2014).101.Wang, Z. et al. Restoration from extreme H7N9 illness is related to numerous response mechanisms dominated by CD8+ T cells. Nat. Commun. 6, 6833 (2015).This manuscript supplies proof that early cross-reactive CD8
+ T cell immunity performs an essential half in restoration from extreme avian influenza A H7N9 virus-induced illness.102.van de Sandt, C. E. et al. Human influenza A virus-specific CD8+ T cell response is long-lived. J. Infect. Dis. 212, 81–85 (2015).103.Solar, J. C. & Bevan, M. J. Faulty CD8 T cell reminiscence following acute an infection with out CD4 T cell assist. Science 300, 339–342 (2003).104.McKinstry, Ok. Ok. et al. Reminiscence CD4+ T cells shield in opposition to influenza by a number of synergizing mechanisms. J. Clin. Make investments. 122, 2847–2856 (2012).105.Deliyannis, G. et al. Intranasal lipopeptide primes lung-resident reminiscence CD8+ T cells for long-term pulmonary safety in opposition to influenza. Eur. J. Immunol. 36, 770–778 (2006).106.Pejoski, D., Zeng, W., Rockman, S., Brown, L. E. & Jackson, D. C. A lipopeptide primarily based on the M2 and HA proteins of influenza A viruses induces protecting antibody. Immunol. Cell. Biol. 88, 605–611 (2010).107.McMichael, A. J., Gotch, F. M., Noble, G. R. & Beare, P. A. Cytotoxic T cell immunity to influenza. N. Engl. J. Med. 309, 13–17 (1983).108.Topham, D. J., Tripp, R. A. & Doherty, P. C. CD8+ T cells clear influenza virus by perforin or Fas-dependent processes. J. Immunol. 159, 5197–5200 (1997).109.Doherty, P. C., Turner, S. J., Webby, R. G. & Thomas, P. G. Influenza and the problem for immunology. Nat. Immunol. 7, 449–455 (2006).110.Sridhar, S., Brokstad, Ok. A. & Cox, R. J. Influenza vaccination methods: evaluating inactivated and stay attenuated influenza vaccines. Vaccines three, 373–389 (2015).111.Russ, B. E. et al. Distinct epigenetic signatures delineate transcriptional packages throughout virus-specific CD8+ T cell differentiation. Immunity 41, 853–865 (2014).112.Valkenburg, S. A. et al. Early priming minimizes the age-related immune compromise of CD8+ T cell variety and performance. PLOS Pathog. eight, e1002544 (2012).113.Smith, W., Andrewes, C. H. & Laidlaw, P. P. A virus obtained from influenza sufferers. Lancet 222, 66–68 (1933).This examine describes the primary isolation of influenza virus. Importantly, it consists of proof of safety from influenza virus an infection by passive switch of antibodies within the ferret mannequin of influenza.114.Wrammert, J. et al. Fast cloning of high-affinity human monoclonal antibodies in opposition to influenza virus. Nature 453, 667–671 (2008).115.Gerhard, W., Yewdell, J., Frankel, M. E. & Webster, R. Antigenic construction of influenza virus haemagglutinin outlined by hybridoma antibodies. Nature 290, 713–717 (1981).116.Angeletti, D. et al. Defining B cell immunodominance to viruses. Nat. Immunol. 18, 456–463 (2017).117.Andrews, S. F. et al. Immune historical past profoundly impacts broadly protecting B cell responses to influenza. Sci. Transl Med. 7, 316ra192 (2015).118.Hobson, D., Curry, R. L., Beare, A. S. & Ward-Gardner, A. The function of serum haemagglutination-inhibiting antibody in safety in opposition to problem an infection with influenza A2 and B viruses. J. Hyg. 70, 767–777 (1972).119.Yu, X. et al. Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature 455, 532–536 (2008).120.Novel Swine-Origin Influenza A Virus Investigation Staff et al. Emergence of a novel swine-origin influenza A (H1N1) virus in people. N. Engl. J. Med. 360, 2605–2615 (2009).121.Manicassamy, B. et al. Safety of mice in opposition to deadly problem with 2009 H1N1 influenza A virus by 1918-like and classical swine H1N1 primarily based vaccines. PLOS Pathog. 6, e1000745 (2010).122.Steens, A. et al. Age-dependent patterns of an infection and severity explaining the low influence of 2009 influenza A (H1N1): proof from serial serologic surveys within the Netherlands. Am. J. Epidemiol. 174, 1307–1315 (2011).123.Heaton, N. S., Sachs, D., Chen, C. J., Hai, R. & Palese, P. Genome-wide mutagenesis of influenza virus reveals distinctive plasticity of the hemagglutinin and NS1 proteins. Proc. Natl Acad. Sci. USA 110, 20248–20253 (2013).124.Doud, M. B. & Bloom, J. D. Correct measurement of the results of all amino-acid mutations on influenza hemagglutinin. Viruses eight, 155 (2016).125.Monto, A. S., Malosh, R. E., Petrie, J. G. & Martin, E. T. The doctrine of unique antigenic sin: separating good from evil. J. Infect. Dis. 215, 1782–1788 (2017).126.Henry, C., Palm, A. E., Krammer, F. & Wilson, P. C. From unique antigenic sin to the common influenza virus vaccine. Traits Immunol. 39, 70–79 (2017).127.Linderman, S. L. et al. Potential antigenic rationalization for atypical H1N1 infections amongst middle-aged adults in the course of the 2013–2014 influenza season. Proc. Natl Acad. Sci. USA 111, 15798–15803 (2014).128.Li, Y. et al. Immune historical past shapes specificity of pandemic H1N1 influenza antibody responses. J. Exp. Med. 210, 1493–1500 (2013).129.Krammer, F. & Palese, P. Influenza virus hemagglutinin stalk-based antibodies and vaccines. Curr. Opin. Virol. three, 521–530 (2013).130.Ekiert, D. C. & Wilson, I. A. Broadly neutralizing antibodies in opposition to influenza virus and prospects for common therapies. Curr. Opin. Virol. 2, 134–141 (2012).131.Neirynck, S. et al. A common influenza A vaccine primarily based on the extracellular area of the M2 protein. Nat. Med. 5, 1157–1163 (1999).132.Wohlbold, T. J. et al. Broadly protecting murine monoclonal antibodies in opposition to influenza B virus goal extremely conserved neuraminidase epitopes. Nat. Microbiol. 2, 1415–1424 (2017).133.Wan, H. et al. Molecular foundation for broad neuraminidase immunity: conserved epitopes in seasonal and pandemic H1N1 in addition to H5N1 influenza viruses. J. Virol. 87, 9290–9300 (2013).134.Rajendran, M. et al. Evaluation of anti-influenza virus neuraminidase antibodies in kids, adults, and the aged by ELISA and enzyme inhibition: proof for unique antigenic sin. MBio eight, (2017).135.Wohlbold, T. J. & Krammer, F. Within the shadow of hemagglutinin: a rising curiosity in influenza viral neuraminidase and its function as a vaccine antigen. Viruses 6, 2465–2494 (2014).136.DiLillo, D. J., Palese, P., Wilson, P. C. & Ravetch, J. V. Broadly neutralizing anti-influenza antibodies require Fc receptor engagement for in vivo safety. J. Clin. Make investments. 126, 605–610 (2016). This examine demonstrates that immune responses induced in opposition to the conserved influenza virus HA stalk area embrace broadly protecting antibodies that activate effector cells through Fc–FcR interactions.
137.Jegaskanda, S. et al. Cross-reactive influenza-specific antibody-dependent mobile cytotoxicity antibodies within the absence of neutralizing antibodies. J. Immunol. 190, 1837–1848 (2013).138.Jegaskanda, S., Weinfurter, J. T., Friedrich, T. C. & Kent, S. J. Antibody-dependent mobile cytotoxicity is related to management of pandemic H1N1 influenza virus an infection of macaques. J. Virol. 87, 5512–5522 (2013).139.Seibert, C. W. et al. Recombinant IgA is ample to forestall influenza virus transmission in guinea pigs. J. Virol. 87, 7793–7804 (2013).140.Lowen, A. C. et al. Blocking interhost transmission of influenza virus by vaccination within the guinea pig mannequin. J. Virol. 83, 2803–2818 (2009).141.Ohmit, S. E. & Monto, A. S. Symptomatic predictors of influenza virus positivity in kids in the course of the influenza season. Clin. Infect. Dis. 43, 564–568 (2006).142.Kumar, S. & Henrickson, Ok. J. Replace on influenza diagnostics: classes from the novel H1N1 influenza A pandemic. Clin. Microbiol. Rev. 25, 344–361 (2012).143.Petric, M., Comanor, L. & Petti, C. A. Function of the laboratory in prognosis of influenza throughout seasonal epidemics and potential pandemics. J. Infect. Dis. 194 (Suppl. 2), S98–S110, (2006).144.Newton, D. W., Treanor, J. J. & Menegus, M. A. Scientific and laboratory prognosis of influenza virus infections. Am. J. Manag. Care 6, S265–S275 (2000).145.Dunn, J. J., Woolstenhulme, R. D., Langer, J. & Carroll, Ok. C. Sensitivity of respiratory virus tradition when screening with R-mix recent cells. J. Clin. Microbiol. 42, 79–82 (2004).146.Nie, S. et al. Analysis of Alere i Influenza A&B for speedy detection of influenza viruses A and B. J. Clin. Microbiol. 52, 3339–3344 (2014).147.Merckx, J. et al. Diagnostic accuracy of novel and conventional speedy exams for influenza an infection in contrast with reverse transcriptase polymerase chain response: A scientific evaluation and meta-analysis. Ann. Intern. Med. 167, 394–409 (2017).148.Bhattacharya, S. et al. Transcriptomic biomarkers to discriminate bacterial from nonbacterial an infection in adults hospitalized with respiratory sickness. Sci. Rep. 7, 6548 (2017).149.Salk, J. E. & Suriano, P. C. Significance of antigenic composition of influenza virus vaccine in defending in opposition to the pure illness; observations in the course of the winter of 1947–1948. Am. J. Publ. Well being Nat. Well being 39, 345–355 (1949).150.Plotkin, S. A., Orenstein, W. & Offit, P. (eds), Vaccines sixth edn (Saunders, 2012)151.Rudenko, L., Yeolekar, L., Kiseleva, I. & Isakova-Sivak, I. Improvement and approval of stay attenuated influenza vaccines primarily based on Russian grasp donor viruses: Course of challenges and success tales. Vaccine 34, 5436–5441 (2016).152.Caspard, H., Mallory, R. M., Yu, J. & Ambrose, C. S. Dwell-attenuated influenza vaccine effectiveness in kids from 2009 to 2015-2016: A scientific evaluation and meta-analysis. Open Discussion board Infect. Dis. four, ofx111 (2017).153.Manini, I. et al. Egg-independent influenza vaccines and vaccine candidates. Vaccines 5, 18 (2017).154.Facilities for Illness Management and Prevention. Flublok seasonal influenza (flu) vaccine. CDC (2017).155.Clark, T. W. et al. Trial of 2009 influenza A (H1N1) monovalent MF59-adjuvanted vaccine. N. Engl. J. Med. 361, 2424–2435 (2009).156.Nohynek, H. et al. AS03 adjuvanted AH1N1 vaccine related to an abrupt improve within the incidence of childhood narcolepsy in Finland. PLOS ONE 7, e33536 (2012).157.DiazGranados, C. A. et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N. Engl. J. Med. 371, 635–645 (2014).158.Enami, M., Luytjes, W., Krystal, M. & Palese, P. Introduction of site-specific mutations into the genome of influenza virus. Proc. Natl Acad. Sci. USA 87, 3802–3805 (1990).159.Krammer, F. & Palese, P. Advances within the growth of influenza virus vaccines. Nat. Rev. Drug Discov. 14, 167–182 (2015).160.Paules, C. I., Marston, H. D., Eisinger, R. W., Baltimore, D. & Fauci, A. S. The pathway to a common influenza vaccine. Immunity 47, 599–603 (2017).161.Committee On Infectious Illnesses. Suggestions for prevention and management of influenza in kids, 2017–2018. Pediatrics 140, e20172550 (2017).162.Palese, P. & Wang, T. T. H5N1 influenza viruses: info, not worry. Proc. Natl Acad. Sci. USA 109, 2211–2213 (2012).163.Gomaa, M. R. et al. Avian influenza A(H5N1) and A(H9N2) seroprevalence and threat elements for an infection amongst Egyptians: a potential, managed seroepidemiological examine. J. Infect. Dis. 211, 1399–1407 (2015).164.Wang, T. T., Parides, M. Ok. & Palese, P. Seroevidence for H5N1 influenza infections in people: meta-analysis. Science 335, 1463 (2012).165.Varble, A. et al. Influenza A virus transmission bottlenecks are outlined by an infection route and recipient host. Cell Host Microbe 16, 691–700 (2014).166.Sobel Leonard, A., Weissman, D. B., Greenbaum, B., Ghedin, E. & Koelle, Ok. Transmission bottleneck dimension estimation from pathogen deep-sequencing information, with an software to human influenza A virus. J. Virol. 91, e00171-17 (2017).167.Osterholm, M. T., Kelley, N. S., Sommer, A. & Belongia, E. A. Efficacy and effectiveness of influenza vaccines: a scientific evaluation and meta-analysis. Lancet Infect. Dis. 12, 36–44 (2012).168.DiazGranados, C. A., Denis, M. & Plotkin, S. Seasonal influenza vaccine efficacy and its determinants in kids and non-elderly adults: a scientific evaluation with meta-analyses of managed trials. Vaccine 31, 49–57 (2012).169.Beyer, W. E. et al. Reply: Letter to the editor, Cochrane rearranged. Vaccine 33, 13–14 (2015).170.Facilities for Illness Management and Prevention. ACIP votes down use of LAIV for 2016–2017 flu season. CDC (2016).171.Saito, N. et al. Destructive influence of prior influenza vaccination on present influenza vaccination amongst individuals contaminated and never contaminated in prior season: a test-negative case-control examine in Japan. Vaccine 35, 687–693 (2017).172.Paules, C. I., Sullivan, S. G., Subbarao, Ok. & Fauci, A. S. Chasing seasonal influenza – the necessity for a common influenza vaccine. N. Engl. J. Med. 378, 7–9 (2018).173.Hata, A., Akashi-Ueda, R., Takamatsu, Ok. & Matsumura, T. Security and efficacy of peramivir for influenza remedy. Drug. Des. Dev. Ther. eight, 2017–2038 (2014).174.McKimm-Breschkin, J. L. Influenza neuraminidase inhibitors: antiviral motion and mechanisms of resistance. Influenza Different Respir. Viruses 7 (Suppl. 1), 25–36 (2013).175.Okoli, G. N., Otete, H. E., Beck, C. R. & Nguyen-Van-Tam, J. S. Use of neuraminidase inhibitors for speedy containment of influenza: a scientific evaluation and meta-analysis of particular person and family transmission research. PLOS ONE 9, e113633 (2014).176.Muthuri, S. G. et al. Effectiveness of neuraminidase inhibitors in decreasing mortality in sufferers admitted to hospital with influenza A H1N1pdm09 virus an infection: a meta-analysis of particular person participant information. Lancet Respir. Med. 2, 395–404 (2014).177.Dobson, J., Whitley, R. J., Pocock, S. & Monto, A. S. Oseltamivir remedy for influenza in adults: a meta-analysis of randomised managed trials. Lancet 385, 1729–1737 (2015).178.Venkatesan, S. et al. Impression of outpatient neuraminidase inhibitor remedy in sufferers contaminated with influenza A(H1N1)pdm09 at excessive threat of hospitalization: a person participant information metaanalysis. Clin. Infect. Dis. 64, 1328–1334 (2017).179.Deyde, V. M. et al. Surveillance of resistance to adamantanes amongst influenza A(H3N2) and A(H1N1) viruses remoted worldwide. J. Infect. Dis. 196, 249–257 (2007).180.Gubareva, L. V. et al. Complete evaluation of 2009 pandemic influenza A (H1N1) virus drug susceptibility in vitro. Antivir. Ther 15, 1151–1159 (2010).181.Meijer, A. et al. Oseltamivir-resistant influenza virus A (H1N1), Europe, 2007–2008 season. Emerg. Infect. Dis. 15, 552–560 (2009).182.Bloom, J. D., Gong, L. I. & Baltimore, D. Permissive secondary mutations allow the evolution of influenza oseltamivir resistance. Science 328, 1272–1275.183.Abed, Y., Pizzorno, A., Bouhy, X. & Boivin, G. Function of permissive neuraminidase mutations in influenza A/Brisbane/59/2007-like (H1N1) viruses. PLOS Pathog. 7, e1002431 (2011).184.Okomo-Adhiambo, M. et al. Oseltamivir-resistant influenza A(H1N1)pdm09 viruses, United States, 2013–2014. Emerg. Infect. Dis. 21, 136–141 (2015).185.Operario, D. J., Moser, M. J. & St George, Ok. Extremely delicate and quantitative detection of the H274Y oseltamivir resistance mutation in seasonal A/H1N1 influenza virus. J. Clin. Microbiol. 48, 3517–3524 (2010).186.Memoli, M. J., Hrabal, R. J., Hassantoufighi, A., Eichelberger, M. C. & Taubenberger, J. Ok. Fast choice of oseltamivir- and peramivir-resistant pandemic H1N1 virus throughout remedy in 2 immunocompromised hosts. Clin. Infect. Dis. 50, 1252–1255 (2010).187.Whitley, R. J. et al. World evaluation of resistance to neuraminidase inhibitors, 2008-2011: the Influenza Resistance Info Research (IRIS). Clin. Infect. Dis. 56, 1197–1205 (2013).188.Butler, J. et al. Estimating the health benefit conferred by permissive neuraminidase mutations in current oseltamivir-resistant A(H1N1)pdm09 influenza viruses. PLOS Pathog. 10, e1004065 (2014).189.Meijer, A. et al. World replace on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2012–2013. Antiviral Res. 110, 31–41 (2014).190.Yamashita, M. Laninamivir and its prodrug, CS-8958: long-acting neuraminidase inhibitors for the remedy of influenza. Antivir. Chem. Chemother. 21, 71–84 (2010).191.Furuta, Y. et al. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res. 100, 446–454 (2013).192.Clark, M. P. et al. Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2. J. Med. Chem. 57, 6668–6678 (2014).193.Portsmouth, S., Kawaguchi, Ok., Arai, M., Tsuchiya, Ok. & Uehara, T. Cap-dependent endonuclease inhibitor S-033188 for the remedy of influenza: outcomes from a part three, randomized, double-blind, placebo- and active-controlled examine in in any other case wholesome adolescents and adults with seasonal influenza. Open Discussion board Infect. Dis. four, S744 (2017). This paper stories scientific trial outcomes of baloxavir marboxil, a brand new influenza drug authorized in Japan in 2018.194.Haffizulla, J. et al. Impact of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, part 2b/three trial. Lancet Infect. Dis. 14, 609–618 (2014).195.Beigel, J. H. et al. Immune plasma for the remedy of extreme influenza: an open-label, multicentre, part 2 randomised examine. Lancet Respir. Med. 5, 500–511 (2017).196.Hung, I. F. N. et al. Hyperimmune IV immunoglobulin remedy: a multicenter double-blind randomized managed trial for sufferers with extreme 2009 influenza A(H1N1) an infection. Chest 144, 464–473 (2013).197.Koszalka, P., Tilmanis, D. & Damage, A. C. Influenza antivirals presently in late-phase scientific trial. Influenza Different Respir. Viruses 11, 240–246 (2017).198.Torner, N. et al. Effectiveness of non-pharmaceutical measures in stopping pediatric influenza: a case-control examine. BMC Publ. Well being 15, 543 (2015).199.Halloran, M. E. et al. Modeling focused layered containment of an influenza pandemic in america. Proc. Natl Acad. Sci. USA 105, 4639–4644 (2008).200.Fiore, A. E. et al. Antiviral brokers for the remedy and chemoprophylaxis of influenza — suggestions of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep. 60, 1–24 (2011).201.Uyeki, T. Antiviral remedy for sufferers hospitalized with 2009 pandemic influenza A (H1N1). N. Engl. J. Med. 361, e110 (2009).202.Stewart, R. J. et al. Influenza antiviral prescribing for outpatients with an acute respiratory sickness and at excessive threat for influenza-associated issues throughout 5 influenza seasons-United States, 2011–2016. Clin. Infect. Dis. 66, 1035–1041 (2018).203.Oboho, I. Ok. et al. Oseltamivir use amongst kids and adults hospitalized with community-acquired pneumonia. Open Discussion board Infect. Dis. four, ofw254 (2017).204.Coleman, B. L. et al. Pre-and post-pandemic tendencies in antiviral use in hospitalized sufferers with laboratory-confirmed influenza: 2004/05-2013/14, Toronto, Canada. Antiviral Res. 140, 158–163 (2017).205.Hung, I. F. N. et al. Efficacy of clarithromycin-naproxen-oseltamivir mixture within the remedy of sufferers hospitalized for influenza A(H3N2) an infection: an open-label randomized, managed, part IIb/III trial. Chest 151, 1069–1080 (2017).206.Sims, L. D. Intervention methods to scale back the chance of zoonotic an infection with avian influenza viruses: scientific foundation, challenges and data gaps. Influenza Different Respir. Viruses 7 (Suppl. 2), 15–25 (2013).207.Domenech, J. et al. Experiences with vaccination in nations endemically contaminated with extremely pathogenic avian influenza: the Meals and Agriculture Group perspective. Rev. Sci. Tech. 28, 293–305 (2009).208.Ellis, T. M. et al. Use of avian influenza vaccination in Hong Kong. Dev. Biol. 124, 133–143 (2006).209.Leung, Y. H. et al. Avian influenza and ban on in a single day poultry storage in stay poultry markets, Hong Kong. Emerg. Infect. Dis. 18, 1339–1341 (2012).210.Lau, E. H. et al. Impact of interventions on influenza A (H9N2) isolation in Hong Kong’s stay poultry markets, 1999–2005. Emerg. Infect. Dis. 13, 1340–1347 (2007).211.Bao, C. J. et al. Dwell-animal markets and influenza A (H7N9) virus an infection. N. Engl. J. Med. 368, 2337–2339 (2013).212.Chambers, T. M., Dubovi, E. J. & Donis, R. O. in Textbook of Influenza 2nd edn (eds Webster, R. G., Monto, A. S., Braciale, T. J. & Lamb, R. A.) (Blackwell Science, Oxford, 2013).213.Nichol, Ok. L., D’Heilly, S. J., Greenberg, M. E. & Ehlinger, E. Burden of influenza-like sickness and effectiveness of influenza vaccination amongst working adults aged 50–64 years. Clin. Infect. Dis. 48, 292–298 (2009).214.Gozalo, P. L., Pop-Vicas, A., Feng, Z., Gravenstein, S. & Mor, V. Impact of influenza on practical decline. J. Am. Geriatr. Soc. 60, 1260–1267 (2012).215.Molinari, N. A. et al. The annual influence of seasonal influenza within the US: measuring illness burden and prices. Vaccine 25, 5086–5096 (2007).216.Rello, J. & Pop-Vicas, A. Scientific evaluation: major influenza viral pneumonia. Crit. Care 13, 235 (2009).217.Morens, D. M., Taubenberger, J. Ok. & Fauci, A. S. Predominant function of bacterial pneumonia as a reason for demise in pandemic influenza: implications for pandemic influenza preparedness. J. Infect. Dis. 198, 962–970 (2008).218.Chien, Y. W., Klugman, Ok. P. & Morens, D. M. Bacterial pathogens and demise in the course of the 1918 influenza pandemic. N. Engl. J. Med. 361, 2582–2583 (2009).219.Morris, D. E., Cleary, D. W. & Clarke, S. C. Secondary bacterial infections related to influenza pandemics. Entrance. Microbiol. eight, 1041 (2017).220.Taubenberger, J. Ok. & Morens, D. M. The pathology of influenza virus infections. Annu. Rev. Pathol. three, 499–522 (2008).221.Agyeman, P., Duppenthaler, A., Heininger, U. & Aebi, C. Influenza-associated myositis in kids. An infection 32, 199–203 (2004).222.MacDonald, Ok. L. et al. Poisonous shock syndrome. A newly acknowledged complication of influenza and influenzalike sickness. JAMA 257, 1053–1058 (1987).223.Steininger, C. et al. Acute encephalopathy related to influenza A virus an infection. Clin. Infect. Dis. 36, 567–574 (2003).224.Dourmashkin, R. R. What precipitated the 1918–1930 epidemic of encephalitis lethargica? J. R. Soc. Med. 90, 515–520 (1997).225.Zost, S. J. et al. Up to date H3N2 influenza viruses have a glycosylation web site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc. Natl Acad. Sci. USA 114, 12578–12583 (2017).226.Hayden, F. G. Experimental human influenza: observations from research of influenza antivirals. Antivir. Ther. 17, 133–141 (2012).227.Erbelding, E. J. et al. A common influenza vaccine: the strategic plan for the Nationwide Institute of Allergy and Infectious Illnesses. J. Infect. Dis. (2018).228.Freidl, G. S. et al. Influenza on the animal-human interface: a evaluation of the literature for virological proof of human an infection with swine or avian influenza viruses apart from A(H5N1). Euro Surveill. 19 (2014).229.Abdelwhab el, S. M., Veits, J. & Mettenleiter, T. C. Genetic adjustments that accompanied shifts of low pathogenic avian influenza viruses towards greater pathogenicity in poultry. Virulence four, 441–452 (2013).230.World Well being Group. Cumulative variety of confirmed human instances for avian influenza A(H5N1) reported to WHO, 2003–2017. WHO (2017).231.Pantin-Jackwood, M. J. et al. Function of poultry within the unfold of novel H7N9 influenza virus in China. J. Virol. 88, 5381–5390 (2014).232.World Well being Group. Human an infection with avian influenza A(H7N9) virus – China. WHO (2017).233.Imai, M. et al. A extremely pathogenic avian H7N9 influenza virus remoted from A human is deadly in some ferrets contaminated through respiratory droplets. Cell Host Microbe 22, 615–626 (2017).234.Li, C. et al. Evolution of H9N2 influenza viruses from home poultry in Mainland China. Virology 340, 70–83 (2005).235.Lam, T. T. et al. The genesis and supply of the H7N9 influenza viruses inflicting human infections in China. Nature 502, 241–244 (2013).236.Palese, P., Tumpey, T. M. & García-Sastre, A. What can we be taught from reconstructing the extinct 1918 pandemic influenza virus? Immunity 24, 121–124 (2006).237.Matthey, S. et al. Fast detection of respiratory viruses by shell vial tradition and direct staining by utilizing pooled and particular person monoclonal antibodies. J. Clin. Microbiol. 30, 540–544 (1992).238.Loeffelholz, M. J. et al. Comparability of the FilmArray Respiratory Panel and Prodesse real-time PCR assays for detection of respiratory pathogens. J. Clin. Microbiol. 49, 4083–4088 (2011).239.Teo, J. et al. VereFlu: an built-in multiplex RT-PCR and microarray assay for speedy detection and identification of human influenza A and B viruses utilizing lab-on-chip know-how. Arch. Virol. 156, 1371–1378 (2011).240.Kim, D. Ok. & Poudel, B. Instruments to detect influenza virus. Yonsei Med. J. 54, 560–566 (2013).241.Damage, A. C., Alexander, R., Hibbert, J., Deed, N. & Barr, I. G. Efficiency of six influenza speedy exams in detecting human influenza in scientific specimens. J. Clin. Virol. 39, 132–135 (2007).


Please enter your comment!
Please enter your name here