Citations are organized by date. Landmark references are noted with an annotation “(LANDMARK).”
The Influenza Epidemic. J Natl Med Assoc. 1918, 10(3):126-52.
This article is the first mention of the 1918 epidemic, as termed “influenza,” in the literature available today. It is certainly possible that it appeared elsewhere under other names, or in literature no longer readily accessible.
Robertson, W.F. Influenza: Its Cause and Prevention. Br Med J. 1918, 2(3025):680-681.
This paper from 1918 discusses the best methods for growing the “bacillus of influenza,” a microbe frequently found in the respiratory tracts of individuals with influenza which was believed to be the causative agent of the influenza disease phenotype. It also discusses preliminary bacillus vaccination protocols and chronic infection with the bacillus of influenza.
Gibson, H.G., and Connor, J.I. A filterable virus as the cause of the early stage of the present epidemic influenza. Br Med J. 1918, 2(3024):645-646. (LANDMARK)
Here, the authors build off of a previous experiment to demonstrate that the causative agent of influenza passed through filters with pores small enough to retain bacteria. This was a common practice during this time to investigate microbial infections, and although this was not the first time this method appears for influenza in the literature, it is the definitive report of the 1918 influenza strains viral identity. These authors later confirm this in a more detailed but less novel publication of similar findings (ref.).
Shope, R.E. Studies on Immunity to Swine Influenza. J Exp Med. 1932, 56(4):575-85.
This study further confirmed a filtered virus as the causative agent of influenza infection. The author also demonstrates that intramuscular injection of the virus does not produce infection in pigs, but does provide immunity – a finding with important implications in vaccine development. This paper also identifies a direct relationship between influenza infection and respiratory cells.
Smith, W., Andrewes, C.H., and Laidlaw, P.P. [Reviewed] Timbury, M.C. A Virus obtained from influenza Patients. Reviews in Medical Virology. 1995*, 5:187-191. (LANDMARK)
This paper presents the first isolation of the influenza A virus (H1N1, although the authors were unaware of this at the time) by filtration of throat washings from infected individuals. They demonstrate that this leads to infection in ferrets, and that influenza infection can be prevented by treatment with serum of a recovered animal. Their findings also suggest that the virus is localized to the respiratory tract, as filtrates from other organ systems do not produce disease in ferrets. (*Note: This paper was published in 1995, but is a reprint of the 1933 article which was not available elsewhere)
Francis, T. Jr. Transmission of Influenza by a Filterable Virus. Science. 1934, 80(2081):457-59.
This study confirms the findings of Shope and others that the causative agent of influenza is a virus. These studies are conducted in mice, and more thorough than previous work. Additionally, the author states that infection was able to be produced from bacteriologically sterile samples, further confirming these findings.
Taylor, A.R., Sharp, D.G., McLean, I.W., Beard, D., Beard, J.W., Dingle, J.H., and Feller, E. Jr. Purification and Character of the Swine Influenza Virus. Science. 1943, 98(2557):587-89. (LANDMARK)
This article presents purification and study of the Swine Influenza Virus (H1N1) by electron micrographs and chemical analysis. The authors describe the virus as a lipoprotein complex, and characterize its size and chemical composition.
Hirst, G.K. Adsorption of Influenza Virus on Cells of the Respiratory Tract. J Exp Med. 1943, 78(2):99-109.
Here, the author demonstrates that respiratory cells readily uptake intratracheally administered influenza virus (discusses both types A and B). He states that his results may suggest destruction of a specific receptor substance necessary for infection, which may involve an enzymatic reaction. This is an important step in understanding infection mechanisms with this virus.
Burnet, F.M.; and Lind, P.E. A genetic approach to variation in influenza viruses; recombination of characters between the influenza virus A strain NWS and strains of different serological types. J Gen Microbiol. 1951, 5(1):67-82. (LANDMARK)
These authors demonstrated that influenza viruses can recombine to form novel strains on coinfection.
Baron, S., and Jensen, K.E. Evidence for Genetic Interaction Between Non-infectious and Infectious Influenza A Viruses. J Exp Med. 1955, 102(6):677-97.
These authors demonstrate that non-infectious influenza viruses retain the ability to genetically recombine on coinfection with other viruses longer than their infective counterparts. This is an evolutionary asset to the virus, posing opportunities to enhance its variation and infectivity.
Henderson, J.R., and Kempf, J.E. Intracellular proteins associated with the synthesis of the influenza A virus. Virology. 1959, 9(1):72-83.
View Abstract Here (Full Article in Trexler Reserves)
This study investigates proteins isolated from influenza-infected cell extracts, identifying a number of small, non-infectious proteins which the authors hypothesize play a role in viral synthesis within the cell.
Van Hoosier Jr., G.L. Serological characteristics of some 1960 strains of swine influenza virus. Bull World Health Organ. 1962, 26(2):304-05.
Here, the author identifies influenza viral strains present in tracheal and blood samples collected from swine, in hopes of understanding the circulating seasonal strains. Strains were identified by the haemagglutination-inhibition test.
Kilbourne, E.D., Laver, W.G., Schulman, J.L., and Webster, R.G. Antiviral activity of antiserum specific for an influenza virus neuraminidase. J. Virol. 1968, 2(4):281-88. (LANDMARK)
Though not specific to H1N1, this article presents important immunological investigation with the H0N2 variant of clinical relevance to all influenza A strains. The authors produce antiserum specific to the neuraminidase protein which inhibits neuraminidase activity in the virus regardless of the hemagglutinin protein identity, and demonstrate that it affects yield and release from infected cells.
Young, J.F., and Palese, P. Evolution of human influenza A viruses in nature: recombination contributes to genetic variation of H1N1 strains. Proc Natl Acad Sci USA. 1979, 76(12):6547-51.
This study demonstrates that the 1977 H1N1 strain shares only HA, NA, M, and NS genes from H1N1 precursors, and that the P1, P2, P3, and NP components were derived from an H3N2 strain. Importantly, this suggests that these viruses are capable not only of mutation, but of recombination in creating new variants.
Palese, P., and Schulman J.L. Mapping of the influenza virus genome: identification of the hemagglutinin and the neuraminidase genes. Proc Natl Acad Sci USA. 1976, 73(6):2142-46. (LANDMARK)
View Here (1/3)
This study uses gel electrophoresis to isolate and identify the RNA components of the influenza genome encoding the HA and NA surface proteins. Though not conducted on H1N1, this information is of extreme importance to all influenza A subtypes.
Palese, P., Ritchey, M.B., and Schulman J.L. Mapping of the influenza virus genome II: identification of the P1, P2, and P3 genes. Proc Natl Acad Sci USA. 1977, 76(1):114-121. (LANDMARK)
View Abstract Here (2/3)
This study serves as a sequel to the previous paper, which identifies the RNA components corresponding to the P1, P2, and P3 proteins using similar techniques as outlined above. (LANDMARK)
Ritchey, M.B., Palese, P., and Schulman J.L. Mapping of the influenza virus genome III: identification of genes coding for nucleoprotein, membrane protein, and nonstructural protein. Journal of Virology. 1976, 20(1):307-313
View Here (3/3)
This study serves as the final component of the previous papers, which identifies the RNA components corresponding to the NP, NS, and MP components, using similar methods as before. This completes the identification of RNA components encoding all core influenza proteins.
Gerhard, W., Yewdell, J., Frankel, M.E., and Webster, R. Antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies. Nature. 1981, 290(5808):713-717. (LANDMARK)
View Abstract Here (Full Text available in Trexler Reserves)
Here, the authors use antibodies to select virus variants expressing mutant HA proteins. This leads to identification of four discrete antigenic sites on the HA proteins which antibodies appear to preferentially bind.
19. McMichael, A.J., Gotch, F.M., Noble, G.R., Beare, P.A. Cytotoxic T-cell immunity to influenza. N Engl J Med. 1983, 309(1):13-17.
In this study, the authors investigate the role of cytotoxic T-cells in preventing and clearing H1N1 influenza infection. Indeed, they demonstrate that cytotoxic T-cell activity is important to recovery from H1N1 infection.
Lucas, W.T., Whitaker-Dowling, P., Kaifer, C.R., and Youngner, J.S. Characterization of a unique protein produced by influenza A virus recovered from a long-term persistent infection. Virology. 1988, 166(2):620-23.
View Abstract Here
In this study, the authors demonstrate that the persistent viral phenotype observed in some individuals is the result of mutation to the NS1 protein. This mutant was initially identified as a novel viral protein, Pi, observed in cases of chronic infection (conducted in H1N1 viral variant).
Weis, W.; Brown, J.H; Cusack, S.; Paulson, J.C.; Skehel, J.J.; and Wiley, D.C. Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid. Nature 1988, 333, 426-431. (LANDMARK)
This article presents the structure of the hemagglutinin protein bound its physiological substrate, sialic acid, solved via x-ray crystallography.
Gorman, O.T., Bean, W.J., Kawaoka, Y., Donatelli, I., Guo, Y.J., and Webster, R.G. Evolution of influenza A virus nucleoprotein genes: implications for the origins of H1N1 human and classical swine viruses. J Virol. 1991, 65(7):3704-14.
This article uses genetic analyses of the NP to track the H1N1 subtype back to a common ancestor originating around 1912-1913.
Nemeroff, M.E., Barabino, S.M.L., Li, Y., Keller, W., and Krug, R.M.Influenza Virus NS1 Protein Interacts with the Cellular 30 kDa Subunit of CPSF and Inhibits 3’ End Formation of Cellular Pre-mRNAs. Mol Cell. 1998, 1(7):991-1000
In this study, the authors demonstrate that the influenza A NS1 protein physically associates with the cellular CPSF protein, a component of the 3’ mRNA-processing machinery. This provides a mechanism by which NS1/influenza A may prevent nuclear export of cellular mRNA transcripts. Viral mRNAs are unaffected, as the are modified by viral proteins, suggesting that this process may serve to divert cellular resources towards viral replication and away from the needs of the cell.
Brown, E.G., and Bailly, J.E. Genetic analysis of mouse-adapted influenza A virus identifies roles for the NA, PB1, and PB2 genes in virulence. Virus Research. 1999, 61(1):63-76. (LANDMARK)
Here, the authors identify gain of function mutations to the PB1, PB2, NA, HA (not novel), and M1 (not novel) genes which increase replication and virulence of the pathogen. They believe these may correspond to a structural motif which may be of therapeutic potential in antiviral development.
Lecoq, H. Discovery of the First Virus, the Tobacco Mosaic Virus: 1892 or 1898? C R Acad Sci III. 2001, 324(10):929-933.
This review provides an account of the discovery and early investigation of the Tobacco Mosaic Virus, generally regarded as the birth of virology. This research was important to identification of the causative agent as viral for influenza.
Mañes, S; del Real, G.; and Martinez, A. Pathogens: raft hijackers. Nature Rev. Immunology 2003, 3, 557-568.
This article describes the role of lipid rafts in the infection mechanism of many viruses, including the influenza virus.
Stiver, G. The treatment of influenza with antiviral drugs. CMAJ. 2003, 168(1): 49-57.
This review discusses the primary antiviral drugs used in the treatment of influenza infection, including their mechanism of action.
Van Epps, H.L. Influenza: exposing the true killer. J Exp Med. 2006, 203(4): 803.
This review article summarizes the history of the early experiments contributing to the isolation of the influenza virus.
Russell, R.J.; Haire, L.F.; Stevens, D.J.; Collins, P.J.; Lin, Y.P.; Blackburn, G.M.; Hay, A.J.; Gamblin, S.J.; and Skehel, J.J. N1 Neuraminidase (2HTY). PBD 2006.
This is the PBD page for the structure of an N1 neuraminidase protein.
Taubenberger, J.K. and Morens, D.M. The Pathology of Influenza Virus Infections. Annu Rev Pathol 2008 3:499-522.
This review gives account of early pathological and histological characterizations of influenza infections. It also offers a comparison of pandemic and non-pandemic influenzas in this respect.
Brass, A.L.; Huang, I.C.; Benita Y.; et al. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 2009, 139(7):1243-54.
In this study, the authors identify the IFITM protein family as implicated in restriction of infection from multiple prominent human pathogens, including influenza.
Sui, J. et al. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nature Struct and Mol Bio. 2009, 16:265-73.
View Abstract Here
This study identified neutralizing antibodies effective against group 1 influenza viruses, including H1N1, and solved the structure of one such antibody bound the H5 protein. These structural data suggest a mechanism by which these antibodies function in which the heavy chain interferes with a conserved region of the haemagglutinin protein.
Liu, J.; Stevens, D.J.; Haire, L.F.; Walker, P.A.; Coombs, P.J.; Russell, R.J.; Gamblin, S.J.; and Skehel, J.J. Structure of H1 1918 hemagglutinin with human receptor. PBD 2009
This is the PBD page for the structure of the 1918 H1 hemagglutinin protein bound the human sialic acid receptor.
Itoh, Y. et al. In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature. 2009, 460:1021-25. (LANDMARK)
In this study, the authors were interested in exploring what components of the 2009 H1N1 strain (CA04) produced such widespread infection, though it was widely hypothesized that this was in part due to a lack of global immunity to the novel strain. The authors demonstrate that this strain causes more severe pulmonary lesions in mice, but also that it is responsive to certain antiviral drugs, of therapeutic potential.
Allen, I.C.; Scull, M.A.; Moore, C.B.; Holl, E.K.; McElvania-TeKippe E.; Taxman, D.J.; Guthrie, E.H.; Pickles, R.J.; and Ting, J.P. The NLRP3 Inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 2009, 30(4):555-565.
In this article, the authors elucidate the role the NLRP3 inflammasome in recognizing intracellular viral components and restricting viral replication.
Medina, R.A. et al. Pandemic 2009 H1N1 vaccine protects against 1918 Spanish influenza virus. Nature communications. 2010, 1:28.
This study demonstrates that the viral antibodies produced from the 2009 H1N1 vaccination show response to the 1918 H1N1 strain, a result of importance in the case of re-emergence or accidental release of the 1918 variant. Interestingly, they find that the HA proteins between the two strains share a high degree of homology.
Bottcher-Friebertashauser, E.; Freur, C.; Sielaff, F.; Schmidt, S.; Eickmann, M.; Uhlendorff, J.; Steinmetzer, T.; Klenk, H.; and Garten, W. Cleavage of Influenza Virus Hemagglutinin by Airway Proteases TMPRSS2 and HAT Differs in Subcellular Localization And Susceptibility to Protease Inhibitors. J Virol. 2010, 84(11): 5605-5614.
This article demonstrates that available proteases for hemagglutinin determine what cell types the influenza A virus is capable of infecting.
Schroeder, C. Cholesterol-binding viral proteins in virus entry and morphogenesis. Subcell Biochem. 2010, 51:77-108.
This article elucidates the role of cholesterol in the infection mechanisms of multiple viruses, including the influenza virus.
Kaul, K.L.; Mangold, K.A.; Du, H.; Pesavento, K.M.; Nawrocki, J. and Nowak J.A. Influenza A Subtyping. J Mol Diagn 2010 12(5):664-669.
This article discusses an experimental assay used to identify influenza viral subtypes.
Vlahos, R. et al. Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation. PLoS Pathog. 2011, 7(2):e1001271.
Here, the authors identify Nox2-containing NADPH oxidase, a prominent enzymatic source of cellular reactive oxygen species, as playing a significant role in lung inflammation associated with H1N1 influenza infection. Furthermore, they demonstrate that Nox2 shows prominent therapeutic potential in reducing lung inflammation and consequently the severity of disease.
Xu, R.; McBride, R; Nycholat, C.M.; Paulson, J.C.; and Wilson, I.A. Structural Characterization of the Hemagglutinin Receptor Specificity from the 2009 H1N1 Influenza Pandemic. J. Virol. 2011
This paper presents a variety of structures for hemagglutinin proteins bound various sialic acid derivative ligands.
Xu, R.; and Wilson, I.A. Influenza hemagglutinin from the 2009 pandemic in complex with ligand 3SLN. PBD 2012.
This is the PBD for a an H1 hemagglutinin from the 2009 pandemic bound a synthetic ligand.
Everitt, A.R. et al. IFITM3 restricts the morbidity and mortality associated with influenza. Nature. 2012, 484:519-23. (LANDMARK)
This study demonstrates that the IFITM3 protein, an interferon inducible transmembrane protein, is essential for preventing influenza A infection. Single nucleotide polymorphisms to the genes encoding this protein are associated with increased likelihood of severe disease and hospitalization with influenza A infection.
Arranz, R. et al. The Structure of Native Influenza Virion Ribonucleoproteins. Science. 2012, 338(6114):1634-37. (LANDMARK)
The influenza viral genome is made up of RNA units assembled into ribonucleoprotein particles (RNPs), which contain the viral polymerase and nucleoproteins. Here, the authors solve the structure of these RNPs, valuable to understanding the mechanism by which both expression and replication occur in the host cell.
Fukuyama, S. and Kawaoka, Y. The pathogenesis of influenza virus infections: the contributions of virus and host factors. Curr Opin Immunol. 2012 23(4)481-486.
This article discusses a variety of both host and viral factors that confer pathogenesis to the virus.
Jia, R.; Pan, Q.; Ding, S.; Rong, L.; Liu, S.; Geng, Y.; Qiao, W.; and Liang, C. The N-Terminal Region of IFITM3 Modulates Its Antiviral Activity by Regulating IFITM3 Cellular Localization. J. Virology 2012 86 (24): 13697-13707.
This article investigates the role of the IFITM3 protein in restricting influenza infection, following the association of a polymorphism in the IFITM3 gene with increased susceptibility to influenza infection. The authors identify a N-terminal region implicated in localization of IFITM3.
Amini-Bavil-Olyaee, S.; Choi, Y.J.; Lee, J.H.; Shi, M.; Huang, I.; Farzan, M.; and Jung, J.U. The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry. Cell Host Microbe 2013, 13 (4): 452-464.
This article provides a mechanism by which the IFITM3 protein prevents infection by the influenza virus, by interfering with cholesterol homeostasis and localization in the cell.
John, S.P.; Chin, C.R.; Perreira, J.M. et al. The CD225 Domain of IFITM3 Is Required for both IFITM Protein Association and Inhibition of Influenza A Virus and Dengue Virus Replication. J. Virol. 2013, 87(14); 7837-7852.
Here, the authors identify a domain of IFITM3 which is required for its function in preventing viral infection.
Schrauwen, E.J.A.; de Graaf, M.; Herfst, S.; Rimmelzwaan, G.F.; Osterhaus, A.; and Fouchier, R.A.M. Determinants of virulence of influenza A virus. Eur J Clin Microbiol Infect Dis. 2014, 33(4): 479-490.
This review article summarizes identified virulence factors in influenza A viruses, particularly those capable of human infection.
Teijaro, J.R.; Walsh, K.B.; Rice, S.; Rosen, H.; and Micahel, B.A. Mapping the innate signaling cascade essential for cytokine storm during influenza virus infection. PNAS 2014, 111(10): 3799-3804.
This paper investigates the innate immune effectors implicated in the extreme and sometimes harmful host immune response known as a cytokine storm.
Chesarino, N.M.; McMichael, T.M.; Hach, J.C.; and Yount, J.S. Phosphorylation of the Antiviral Protein Interferon-inducible Transmembrane Protein 3 (IFITM3) Dually Regulates Its Endocytosis and Ubiquitination. J. Biol Chem 2014
This paper investigates the role of the IFITM3 protein in restricting influenza infection, following the association of a polymorphism in the IFITM3 gene with increased susceptibility to influenza infection. These authors demonstrate that post translational modifications impact IFITM3 function.
Williams, D.E.; Wu, W.L.; Grotefend, C.R.; Radic, V.; Chung, C.; Chung, Y.H.; Farzan, M.; and Huang, I.C. IFITM3 polymorphism rs12252-C restricts influenza A viruses. PLoS One. 2014, 9(10):e110096.
In this study, the authors demonstrate that the polymorphism variant identified as associated with increased susceptibility to influenza infection is in fact capable of restricting influenza infection.
Cohen, F.S. How Viruses Invade Cells. Biophys J 2016 110(5): 1028-1032.
This review discusses general principles which govern the mechanisms which mediate viral infection of host cells.
Ling, S.; Zhang, C.; Wang, W.; Cai, X.; Yu, L.; Wu, F.; Zhang, L.; and Tian, C. Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3. Nature Sci Reports. 2016. 6, 24029.
This paper investigates the structure of IFITM3, and though it does not present a concrete structure, it does elucidate the transmembrane topology of this protein.
Bahadoran, A.; Lee, S.H.; Wang, S.M.; Manikam, R.; Rajarajeswaran, J.; Raju, C.S.; and Sekaran, S.D. Immune Responses to Influenza Virus and Its Correlation to Age and Inherited Factors. Front Microbiol. 2016, 7:1841.
This article provides a comprehensive review of both innate and adaptive immune factors restricting influenza proliferation in humans.
Sutton, T.C.; Chakraborty, S.; Mallajosyula, V.A.; Lamirande, E.W.; Gganti, K.; Bock, K.W.; Moore, I.N.; Varadarajan, R.; and Subbarao, K. Protective Efficacy of Influenza Group 2 Hemagglutinin Stem-Fragment Immunogen Vaccines. NPJ Vaccines 2017 2:35.
This article explores a conserved HA stalk target as a possible epitope for a universal vaccine.
Yang, C. et al. Influenza A virus upregulates PRPF8 gene expression to increase virus production. Archives of Virology. 2017, 162:1223-1235.
Here, the authors demonstrate that PRPF8, a host cell gene, expression is upregulated during infection with H1N1 by qRT-PCR and western blot analysis. They confirm that PRPF8 plays a role in successful infection and replication of the virus by both overexpressing and knocking out the gene in mice, which produce increased and decreased infection, respectively.
Benet, T. et al. Microorganisms Associated With Pneumonia in Children <5 Years of Age in Developing and Emerging Countries: The GABRIEL Pneumonia Multicenter, Prospective, Case-Control Study. Clin Infect Dis 2017 65(4):604-612.
Here, the authors analyze common microorganisms associated with lower respiratory tract infections.
Dou, D.; Revol, R.; Ostbye, H.; Wang, H.; and Daniels, R. Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement. Front Immunol. 2018, 9: 1581.
This review discusses the cellular mechanisms which drive the influenza lifecycle, including infection and replication.
Krammer, F.; Smith, G. J. D.; Fouchier, R. A. M.; Peiris, M.; Kedzierska, K.; Doherty, P. C.; Palese, P.; Shaw, M. L.; Treanor, J.; Webster, R. G.; et al. Influenza. Nat. Rev. Dis. Primer 2018, 4 (1), 1–21.
This is an extensive review of the Influenza virus. It covers infection mechanisms, transmission, treatment, and clinical symptoms.
Chen, X.; Liu, S.; Goraya, M.U.; Maarouf, M.; Huang, S.; and Chen, J. Host Immune Response to Influenza A Virus Infection. Front Immunol. 2018, 9: 320.
This review provides a comprehensive summary of the innate and adaptive immune response to influenza A virus infection.
Denney, L. and Ho, L. The role of respiratory epithelium in host defence against influenza virus infection. Biomed J. 2018 41(4):218-233.
This article summarizes the role of respiratory epithelial and associated immune cells in preventing influenza virus infection.
Henry, R. and Frederick, M.A. Etymologia: Hemagglutinin and Neuraminidase. Emerg Infec Dis. 2018, 24(10), 1849.
This review provides a brief history of the science surrounding the hemagglutinin and neruaminidase proteins.
Malosh, R.E.; Martin, E.T.; Ortiz, J.R.; and Monto, A.S. The risk of lower respiratory tract infection following influenza virus infection: A systematic and narrative review. Vaccine 2018 36(1):141-147.
This review discusses common factors leading to lower respiratory tract infection secondary to influenza.
Yujie, W. et al. Different Subtypes of Influenza Viruses Target Different Human Proteins and Pathways Leading to Different Pathogenic Phenotypes. Biomed Res Int. 2019.
Here, the authors demonstrate that different subtypes of influenza A target different cellular components on infection. H5N1 NP inhibited TNF-mediated NF-кB activation, while H1N1 had little effect on this pathway. These findings warrant further investigation into infection mechanisms among different influenza A subtypes.
Wellington, D.; Laurenson-Schafer, H.; Abdel-Haq, A.; and Dong, T. IFITM3: How genetics influence influenza infection demographically. Biomedical Journal 2019 42 (1): 19-26.
This article expands on the Nature paper from 2011 which identified a polymorphism in IFITM3 associated with increased susceptibility to influenza infection.
Eisenstein, M. Towards a universal flu vaccine. Nature Outlook. 2019
This article discusses recent scientific advances in the development of a universal influenza vaccine, as well as prospects for the future.
Javitt, G.; and Fass, D. Mucin 2 D3 domain. PBD 2019
This is the PBD page for the structure of a mucin domain. Mucins are implicated in the immune response to the influenza virus.
Cheng, J., Tao, J., Li, B., Shi, Y., and Liu, H. The tyrosine 73 and serine 83 dephosphorylation of H1N1 swine influenza virus NS1 protein attenuates virus replication and induces high levels of beta interferon. Biomed Res Int. 2019, 16:152.
In this study, the authors investigate the role of phosphorylation in the non-structural protein 1 (NS1) of influenza A. They demonstrate that dephosphorylation of Y73 and S83 is detrimental to viral replication and protection from host immune responses. They also identify RIG-I, a cellular RNA virus sensor, as essential to the host IFN-𝛽 response.
van de Sandt, C.E. et al. Challenging immunodominance of influenza-specific CD8+ T cell responses restricted by the restricted by the risk-associated HLA-A*68:01 allomorph. Nature Communications. 2019, 10:5579.
Here, the authors investigate the HLA-A*68:01 allele, associated with increased severity of 2009 H1N1 infection. HLA molecules are associated with activation of CD8+ memory-T-cells, which can respond to conserved viral peptides in cases where a new strain of influenza is encountered. This HLA molecule is associated with presentation of a particularly long peptide, which may limit the effectiveness of the immune response.
Spence, J.S.; He, R.; Hoffman, H.; Das, T.; Thinon, E.; Rice, C.M.; Peng, T.; Chandran, K.; and Hang, H. IFITM3 directly engages and shuttles incoming virus particles to lysosomes. Nature 2019 15, 259-268.
This article investigates the role of the IFITM3 protein in restricting influenza infection, following the association of a polymorphism in the IFITM3 gene with increased susceptibility to influenza infection. The authors propose a partial mechanism for IFITM3 function.
Treanor, J. History of Live, Attenuated Influenza Vaccine. Journal of the Pediatric Infectious Disease Society. 2020, 9(S1):S3-S9.
This review discusses the efficacy and history of live attenuated influenza vaccines (LAIVs) as compared to inactivated influenza vaccines (IIV). It discusses their administration, indications, and mechanisms as well.
UNDATED ONLINE SOURCES
CDC. Types of Influenza Viruses. (Accessed March 12, 2020)
This webpage gives an overview of the influenza viruses relevant to human health.
CDC. Flu Symptoms & Complications (Accessed Mar 12, 2020)
This webpage provides information about common symptoms and clinical outcomes from influenza.
CDC. Influenza (Flu) (Accessed Apr 14, 2020)
This webpage provides general information and resources about the influenza virus.
CDC. Diagnosing Flu (Accessed Mar 12, 2020)
This webpage discusses common techniques used for clinical influenza diagnosis.
KEGG. Influenza A pathway. (Accessed March 12, 2020)
This is the KEGG pathway for influenza A infection and host immune response.
KEGG Enzyme. 18.104.22.168. (Accessed April 14, 2020)
This is the KEGG enzyme page for neuraminidase. This enzyme is responsible for cleaving linkages to the host cell surface during viral budding.
KEGG. Enzyme 22.214.171.124 (cholesterol 25-hydroxylase). (Accessed Apr 20, 2020).
This is the KEGG enzyme page for cholesterol 25-hydroxylase. This enzyme converts cholesterol to 25-HC.
Brain Kart. Anatomy of the Respiratory System (Image). (Accessed Apr 14, 2020)
An image depicting the anatomy of the human respiratory system.
Brief History of the Influenza Virus (Accessed March 27, 2020)
This article describes prominent events in the history of the influenza virus, including major outbreaks.