Functional balance between haemagglutinin and neuraminidase in influenza virus infections
Ralf Wagner
Institut für Virologie, Philipps-Universität, 35011 Marburg, Germany
Search for more papers by this authorMikhail Matrosovich
Institut für Virologie, Philipps-Universität, 35011 Marburg, Germany
M.P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, 142782 Moscow, Russia
Search for more papers by this authorCorresponding Author
Hans-Dieter Klenk
Institut für Virologie, Philipps-Universität, 35011 Marburg, Germany
Institut für Virologie, Philipps-Universität Marburg, Postfach 2360, 35011Marburg, Germany.Search for more papers by this authorRalf Wagner
Institut für Virologie, Philipps-Universität, 35011 Marburg, Germany
Search for more papers by this authorMikhail Matrosovich
Institut für Virologie, Philipps-Universität, 35011 Marburg, Germany
M.P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, 142782 Moscow, Russia
Search for more papers by this authorCorresponding Author
Hans-Dieter Klenk
Institut für Virologie, Philipps-Universität, 35011 Marburg, Germany
Institut für Virologie, Philipps-Universität Marburg, Postfach 2360, 35011Marburg, Germany.Search for more papers by this authorAbstract
Influenza A and B viruses carry two surface glycoproteins, the haemagglutinin (HA) and the neuraminidase (NA). Both proteins have been found to recognise the same host cell molecule, sialic acid. HA binds to sialic acid-containing receptors on target cells to initiate virus infection, whereas NA cleaves sialic acids from cellular receptors and extracellular inhibitors to facilitate progeny virus release and to promote the spread of the infection to neighbouring cells. Numerous studies performed recently have revealed that an optimal interplay between these receptor-binding and receptor-destroying activities of the surface glycoproteins is required for efficient virus replication. An existing balance between the antagonistic HA and NA functions of individual viruses can be disturbed by various events, such as reassortment, virus transmission to a new host, or therapeutic inhibition of neuraminidase. The resulting decrease in the viral replicative fitness is usually overcome by restoration of the functional balance due to compensatory mutations in HA, NA or both proteins. Copyright © 2002 John Wiley & Sons, Ltd.
REFERENCES
- 1Hirst GK. Agglutination of red cells by allantoic fluid of chick embryos infected with influenza virus. Science 1941; 94: 22–23.
- 2Burnet FM, Stone JD. The receptor-destroying enzyme of V. cholerae. Aust J Exp Biol Med 1947; 25: 227–233.
- 3Klenk E, Faillard H, Lempfrid H. Über die enzymatische Wirkung von Influenzaviren. Hoppe-Seylerás Z Physiol Chem 1955; 301: 235–246.
- 4Gottschalk A. Neuraminidase: The specific enzyme of influenza virus and Vibrio cholerae. Biochim Biophys Acta 1957; 23: 645–646.
- 5Herrler G, Rott R, Klenk HD, et al. The receptor-destroying enzyme of influenza C virus is neuraminate-O-acetylesterase. EMBO J 1985; 4: 1503–1506.
- 6Skehel JJ, Wiley DC. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 2000; 69: 531–569.
- 7Colman PM. Structure and function of the neuraminidase. In Textbook of Influenza, KG Nicholson, RG Webster, AJ Hay (eds). Blackwell Science: London, 1998; 65–73.
- 8Rosenthal PB, Zhang X, Formanowski F, et al. Structure of the haemagglutinin-esterase-fusion glycoprotein of influenza C virus. Nature 1998; 396: 92–96.
- 9Ohuchi M, Feldmann A, Ohuchi R, et al. Neuraminidase is essential for fowl plague virus hemagglutinin to show hemagglutinating activity. Virology 1995; 212: 77–83.
- 10Huang RTC, Rott R, Wahn K, et al. The function of the neuraminidase in membrane fusion induced by myxoviruses. Virology 1980; 107: 313–319.
- 11Compans RW, Dimmock NJ, Meier-Ewert H. Effect of antibody to neuraminidase on the maturation and hemagglutinating activity of an influenza A2 virus. J Virol 1969; 4: 528–534.
- 12Palese P, Tobita K, Ueda M, et al. Characterization of temperature sensitive influenza virus mutants defective in neuraminidase. Virology 1974; 61: 397–410.
- 13Griffin JA, Basak S, Compans RW. Effects of hexose starvation and the role of sialic acid in influenza virus release. Virology 1983; 125: 324–334.
- 14Liu C, Eichelberger MC, Compans RW, et al. Influenza type A virus neuraminidase does not play a role in viral entry, replication, assembly, or budding. J Virol 1995; 69: 1099–1106.
- 15Ito T, Kawaoka Y. Host-range barrier of influenza A viruses. Vet Microbiol 2000; 74: 71–75.
- 16Paulson JC. Interactions of animal viruses with cell surface receptors. In The Receptors, vol 2, M Conn (ed.). Academic Press: Orlando, 1985; 131–219.
- 17Connor RJ, Kawaoka Y, Webster RG, et al. Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology 1994; 205: 17–23.
- 18Baum LG, Paulson JC. The N2 neuraminidase of human influenza virus has acquired a substrate specificity complementary to the hemagglutinin receptor specificity. Virology 1991; 180: 10–15.
- 19Kobasa D, Kodihalli S, Luo M, et al. Amino acid residues contributing to the substrate specificity of the influenza A virus neuraminidase. J Virol 1999; 73: 6743–6751.
- 20Lamblin G, Aubert JP, Perini JM, et al. Human respiratory mucins. Eur Respir J 1992; 5: 247–256.
- 21Couceiro JN, Baum LG. Characterization of the hemagglutinin receptor specificity and neuraminidase substrate specificity of clinical isolates of human influenza A viruses. Mem Inst Oswaldo Cruz 1994; 89: 587–591.
- 22Xu G, Suzuki T, Hanagata G, et al. Drift of the sialyl-linkage specific recognition of the sialidase of influenza B virus isolates. J Biochem (Tokyo) 1993; 113: 304–307.
- 23Suzuki T, Horiike G, Yamazaki Y, et al. Swine influenza virus strains recognize sialyl sugar chains containing the molecular species of sialic acid predominantly present in the swine tracheal epithelium. FEBS Lett 1997; 404: 192–196.
- 24Xu G, Suzuki T, Maejima Y, et al. Sialidase of swine influenza A viruses: variation of the recognition specificities for sialyl linkages and for the molecular species of sialic acid with the year of isolation. Glycoconj J 1995; 12: 156–161.
- 25Matrosovich M, Gao P, Kawaoka Y. Molecular mechanisms of serum resistance of human influenza H3N2 virus and their involvement in virus adaptation in a new host. J Virol 1998; 72: 6373–6380.
- 26Schauer R. Chemistry, metabolism, and biological functions of sialic acids. Adv Carbohydr Chem Biochem 1982; 40: 131–234.
- 27Rudneva IA, Kovaleva VP, Varich NL, et al. Influenza A virus reassortants with surface glycoprotein genes of the avian parent viruses: effects of HA and NA gene combinations on virus aggregation. Arch Virol 1993; 133: 437–450.
- 28Rudneva IA, Sklyanskaya EI, Barulina OS, et al. Phenotypic expression of HA-NA combinations in human-avian influenza A virus reassortants. Arch Virol 1996; 141: 1091–1099.
- 29Kaverin NV, Gambaryan AS, Bovin NV, et al. Postreassortment changes in influenza A virus hemagglutinin restoring HA-NA functional match. Virology 1998; 244: 315–321.
- 30Kaverin NV, Matrosovich MN, Gambaryan AS, et al. Intergenic HA-NA interactions in influenza A virus: postreassortment substitutions of charged amino acid in the hemagglutinin of different subtypes. Virus Res 2000; 66: 123–129.
- 31Varghese JN, McKimm-Breschkin JL, Caldwell JB, et al. The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins 1992; 14: 327–332.
- 32von Itzstein M, Wu WY, Kok GB, et al. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 1993; 363: 418–423.
- 33Kim CU, Lew W, Williams MA, et al. Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, sysnthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J Am Chem Soc 1997; 119: 681–690.
- 34Dreitlein WB, Maratos J, Brocavich J. Zanamivir and oseltamivir: two new options for the treatment and prevention of influenza. Clin Ther 2001; 23: 327–355.
- 35Gubareva LV, Kaiser L, Hayden FG. Influenza virus neuraminidase inhibitors. Lancet 2000; 355: 827–835.
- 36McKimm-Breschkin JL. Resistance of influenza viruses to neuraminidase inhibitors – a review. Antiviral Res 2000; 47: 1–17.
- 37Tai CY, Escarpe PA, Sidwell RW, et al. Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS 4071. Antimicrob Agents Chemother 1998; 42: 3234–3241.
- 38McKimm-Breschkin JL, Sahasrabudhe A, Blick TJ, et al. Mutations in a conserved residue in the influenza virus neuraminidase active site decreases sensitivity to Neu5Ac2en-derived inhibitors. J Virol 1998; 72: 2456–2462.
- 39Gubareva LV, Robinson MJ, Bethell RC, et al. Catalytic and framework mutations in the neuraminidase active site of influenza viruses that are resistant to 4-guanidino-Neu5Ac2en. J Virol 1997; 71: 3385–3390.
- 40Bantia S, Ghate AA, Ananth SL, et al. Generation and characterization of a mutant of influenza A virus selected with the neuraminidase inhibitor BCX-140. Antimicrob Agents Chemother 1998; 42: 801–807.
- 41Blick TJ, Sahasrabudhe A, McDonald M, et al. The interaction of neuraminidase and hemagglutinin mutations in influenza virus in resistance to 4-guanidino-Neu5Ac2en. Virology 1998; 246: 95–103.
- 42McKimm-Breschkin JL, Blick TJ, Sahasrabudhe A, et al. Generation and characterization of variants of NWS/G70C influenza virus after in vitro passage in 4-amino-Neu5Ac2en and 4-guanidino-Neu5Ac2en. Antimicrob Agents Chemother 1996; 40: 40–46.
- 43Penn CR, Barnett JM, Bethell RC, et al. Selection of influenza virus with reduced sensitivity in vitro to the neuraminidase inhibitor gg167 (4-guanidino-Neu5Ac2en): changes in hemagglutinin may compensate for the loss of neuraminidase activity. In Options for the Control of Influenza III, LE Brown, AW Hampson, RG Webster (eds). Elsevier Science B.V.: Amsterdam, 1996; 735–740.
- 44Gubareva LV, Matrosovich MN, Brenner MK, et al. Evidence for zanamivir resistance in an immunocompromised child infected with influenza B virus. J Infect Dis 1998; 178: 1257–1262.
- 45Tisdale M. Monitoring of viral susceptibility: new challenges with the development of influenza NA inhibitors. Rev Med Virol 2000; 10: 45–55.
10.1002/(SICI)1099-1654(200001/02)10:1<45::AID-RMV265>3.0.CO;2-R CASPubMedWeb of Science®Google Scholar
- 46Liu C, Air GM. Selection and characterization of a neuraminidase-minus mutant of influenza virus and its rescue by cloned neuraminidase genes. Virology 1993; 194: 403–407.
- 47Hughes MT, Matrosovich M, Rodgers ME, et al. Influenza A viruses lacking sialidase activity can undergo multiple cycles of replication in cell culture, eggs, or mice. J Virol 2000; 74: 5206–5212.
- 48Garcia-Sastre A, Palese P. Genetic manipulation of negative-strand RNA virus genomes. Annu Rev Microbiol 1993; 47: 765–790.
- 49Neumann G, Watanabe T, Ito H, et al. Generation of influenza A viruses entirely from cloned cDNAs. Proc Natl Acad Sci USA 1999; 96: 9345–9350.
- 50Hoffmann E, Neumann G, Kawaoka Y, et al. A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci USA 2000; 97: 6108–6113.
- 51Varghese JN, Laver WG, Colman PM. Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 Å resolution. Nature 1983; 303: 35–40.
- 52Air GM, Laver WG. The neuraminidase of influenza virus. Proteins 1989; 6: 341–356.
- 53Els MC, Air GM, Murti KG, et al. An 18-amino acid deletion in an influenza neuraminidase. Virology 1985; 142: 241–247.
- 54Castrucci MR, Kawaoka Y. Biologic importance of neuraminidase stalk length in influenza A virus. J Virol 1993; 67: 759–764.
- 55Mitnaul LJ, Matrosovich MN, Castrucci MR, et al. Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus. J Virol 2000; 74: 6015–6020.
- 56Wagner R, Wolff T, Herwig A, et al. Interdependence of hemagglutinin glycosylation and neuraminidase as regulators of influenza virus growth: a study by reverse genetics. J Virol 2000; 74: 6316–6323.
- 57Ohuchi M, Ohuchi R, Feldmann A, et al. Regulation of receptor binding affinity of influenza virus hemagglutinin by its carbohydrate moiety. J Virol 1997; 71: 8377–8384.
- 58Baigent SJ, McCauley JW. Glycosylation of haemagglutinin and stalk-length of neuraminidase combine to regulate the growth of avian influenza viruses in tissue culture. Virus Res 2001; 79: 177–185.
- 59Matrosovich M, Zhou N, Kawaoka Y, et al. The surface glycoproteins of H5 influenza viruses isolated from humans, chickens, and wild aquatic birds have distinguishable properties. J Virol 1999; 73: 1146–1155.
- 60Banks J, Speidel ES, Moore E, et al. Changes in the haemagglutinin and the neuraminidase genes prior to the emergence of highly pathogenic H7N1 avian influenza viruses in Italy. Arch Virol 2001; 146: 963–973.