Influenza Virus Neuraminidase: Structure and Function

Обложка

Цитировать

Полный текст

Аннотация

The structure of the influenza virus neuraminidases, the spatial organization of their active site, the mechanism of carbohydrate chains desialylation by neuraminidase, and its role in the influenza virus function at different stages of the viral infectious cycle are considered in this review. Data on the neuraminidase substrate specificity and different approaches in studying the activity of this enzyme are summarized. In addition, data on neuraminidase inhibitors (as antivirals) are provided, along with considerations on the mechanisms of resistance of modern influenza viruses to those antivirals.

Ключевые слова

Полный текст

The influenza virus is an enveloped (-)RN A containing a virus with a segmented genome, and its genetic material is coded by eight RN A-segments. All RN A segments are packed in a nucleocapsid protein, and a complex of polymerase proteins is attached to each of the genomic segments. Those RN A-protein complexes are packed in a lipoprotein envelope lined from the inside with a matrix protein, with haemagglutinin, neuraminidase, and M2 proteins exposed on the outer surface of the viral particle. Neuraminidase is an exosialidase (EC 3.2.1.18) which cleaves -ketosidic linkage between the sialic (N-acetylneuraminic) acid and an adjacent sugar residue [1]. The amino acid sequence of NA is coded by the 6th RN A segment. Nine subtypes of NA are described for influenza A, whereas only one NA subtype was revealed for the influenza viruses B and C [2]. Nine subtypes of influenza A NA are divided into two phylogenic groups. The first group consists of the neuraminidases of N1, N4, N5 and N8 subtypes, and the second one consists of N2, N3, N6 N7 and N9 subtypes [3]. The enzyme of the influenza C virus does not belong to the neuraminidase group. It promotes the O-deacetylation of the N-acetyl-9-O-acetylneuraminic acid, i.e. it belongs to the esterase family and will not be considered in this review.
×

Список литературы

  1. Varghese J.N., Colman P.M. Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2 A resolution. // J. Mol. Biol. 221: 473-486 (1991).
  2. Colman P.M. NA enzyme and antigen. // In The influenza viruses (R. M. Krug, ed.). Plenum Publishing Corporation, New York: 175-218 (1989).
  3. Russell R.J., Haire L.F., Stevens D.J., Collins P.J., Lin Y.P., Blackburn G.M., Hay A.J., Gamblin S.J., Skehel J.J. The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. // Nature 44: 45-49 (2006).
  4. Harris A., Cardone G., Winkler D.C., Heymann J.B., Brecher M., White J.M., Steven A.C. Influenza virus pleiomorphy characterized by cryoelectron tomography. // PNAS :19123-19127 (2006).
  5. Varghese J.N., Colman P.M., van Donkelaar A., Blick T.J., Sharasrabudhi A., McKimmBreschkin J.L. Structural evidence for a second sialic acid binding site in avian influenza virus neuraminidases. // Biochemistry. 94: 11808-11812 (1997).
  6. Bossart-Whitaker P., Carson M., Babu Y.S., Smith C.D., Laver W.G., Air G.M. Threedimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy-2,3-dehydro-N-acetyl neuraminic acid. // J. Mol. Biol. 232: 1069-1083 (1993).
  7. Janakiraman M.N., White C.L., Laver W.G., Air G.M., Luo M. Structure of influenza virus neuraminidase B/Lee/40 complexed vith sialitic acid and dehydro analog at 1.8-A resolution: implications for the catalytic mechanism. // Biochemistry. 33: 8172-8179 (1994).
  8. Takahashi T., Suzuki T., Hidari K.I-P.J., Miyamoto D., Suzuki Y. A molecular mechanism for the low-pH stability of sialidase activity of influenza A virus N2 neuraminidases. // FEBS Lett. 543: 71-75 (2003).
  9. Colman P.M., Hoyne P.A., Lawrence M.C. Sequence and structure alignment of paramyxovirus hemagglutinin-neuraminidase with influenza virus neuraminidase. // J. Virol. 67: 2972-2980 (1993).
  10. Varghese J.N., Colman P.M., van Donkelaar A., Blick T.J., Sharasrabudhi A., McKimm-Breschkin J.L. Structural evidence for a second sialic acid binding site in avian influenza virus neuraminidases. // Biochemistry. 94: 11808-11812 (1997).
  11. Matrosovich M.N., Krauss S., Webster R.G. H9N2 influenza A viruses from poultry in Asia have human virus-like receptor specificity. // Virol. 281: 56-162 (2001).
  12. Li S., Schulman J., Itamura S., Palese P. Glycosylation of neuraminidase determines the neurovirulence of influenza A/WSN/33 virus. // J. Virol. 67: 6667-6673 (1993).
  13. Saito T., Kawano K. Loss of glycosylation at Asn144 alters the substrate preference of the N8 influenza A virus neuraminidase. // J. Vet. Med. Sci. 59: 923-926 (1997).
  14. von Itzstein M., Wu W.-Y., Kok G.B., Pegg M.S., Dyason J.C., Jin B., Phan T.V., Smythe M.L., White H.F., Oliver S.W., Colman P.M., Varghese J.N., Ryan D.M., Woods J.M., Bethel R.C., Hotham V.J., Cameron J.M., Penn C.R. Rational design of potent sialidasebased inhibitors of influenza virus replication. // Nature 363: 418-423 (1993).
  15. Watts A.G., Oppezzo P., Withers S.G., Alzari P.M., Buschiazzo A. Structural and kinetic analysis of two covalent sialosyl-enzymeintermediates on Trypanosoma rangeli sialidase // J. Biol. Chem. 281: 4149-4155 (2006).
  16. von Itzstein M. The war against influenza: discovery and development of sialidase inhibitors. // Nat Rev Drug Discov. 6: 967-74 (2007).
  17. Watts A.G., Withers S.G. The synthesis of some mechanistic probes for sialic acid processing enzymes and the labeling of a sialidase from Trypanosoma rangeli. // Can. J. Chem. 82: 1581-1588 (2004).
  18. Colman P.M., Smith B.J. The trypanosomal trans-sialidase: two catalytic functions associated with one catalytic site. // Structure 10: 1466-1468 (2002).
  19. Oxford J.S., Bossuyt S., Eswarasaran R., Lambkin R. Drugs to combat the epidemic and pandemic faces of influenza. // In Influenza (C.W. Potter ed.) Elsevier: 201-234 (2002).
  20. Hanessian S., Wang J., Montgomery D., Stoll V., Stewart K.D., Kati W., Maring C., Kempf D., Hutchins C., Laver W.G. Design, synthesis, and neuraminidase inhibitory activity of GS-4071 analogues that utilize a novel hydrophobic paradigm. // Bioorg. Med. Chem. Lett. 12: 3425-3429 (2002).
  21. Babu Y.S., Chad P., Bantia S., Kotian P., Dehgani A., El-Kattan Y., Lin T.-H., Hutchson T.L., Elliot A., Parker C., Ananth S., Horn LaSun L., Laver G., Montgomery J. BCX-1812 (RWJ-270201): discovery of a novel highly potent, orally active, and selective influenza neuraminidase inhibitor through structure-based drug design. // J. Med. Chem. 43: 3482-3486 (2000).
  22. Bianco A., Brufani M., Dri D.A., Melchioni C., Filocamo L. Design and synthesis of a new furanosic sialylmimetic as a potential influenza neuraminidase inhibitor. // Letters in Organic Chemistry 2: 83-88 (2005).
  23. Blick T.J., Sahasrabudhe A., McDonald M., Owens I.J., Morley P.J., Fenton R.J., McKimm-Breschkin J.L. The interaction of hemagglutinin and neuraminidase mutations in influenza virus in resistance to 4-guanidino-Neu5Ac2en. // Virol. 246: 95-103 (1998).
  24. Lackenby A., Hungnes O., Dudman S.G., Meijer A., Paget W.J., Hay A.J., Zambon M.C. Emergence of resistance to oseltamivir among influenza A (H1N1) viruses in Europe // EUROSURVEILLANCE 13: – 2 (2008).
  25. Hui-Ling Yen, Ilyushina N.A., Salomon R., Hoffmann E., Webster R.G., Govorkova E.A. Neuraminidase inhibitor-resistant recombinant A/Vietnam/1203/04 (H5N1) influenza viruses retain their replication efficiency and pathogenicity in vitro and in vivo // J. of Virol. 81: 12418 – 12426 (2007).
  26. Matrosovich M., Matrosovich T.,Gray T., Roberts N.A., Klenk H.-D., Neuraminidase is important for the initiation of influenza virus infection in human airway epitelium./J.Virol. 78: 12665-12667 (2004).
  27. Wagner R., Wolf T., Herwig A., Pleschka S., Klenk H.-D. Interdependence of hemagglutinin glycosylation and neuraminidase as regulators of influenza growth: a study by reverse genetics. // J. Virol. 74: 6316-6323 (2000).
  28. Ohuchi M., Feldmann A., Ohuchi R., Klenk H.-D. Neuraminidase is essential for fowl plague virus hemagglutinin to show hemagglutinating activity. Virology. 10;212(1):7783 (1995). Rudneva I.A., Kovaleva V.P., Varich N.L., Farashyan V.29. R., Gubareva L V., Yamnikova S.S., Popova I.A., Presnova V.P., Kaverin N.V. Influenza A virus reassortants with surface glycoprotein genes of avian parent viruses: effects of HA and NA gene combinations on virus aggregation. // Arch. Virol. 133: 437-450 (1993).
  29. Rudneva I.A., Sklyanskaya E.I., Barulina O.S., Yamnikova S.S., Kovaleva V.P., Tsvetkova I.V., Kaverin N.V.. Phenotypic expression of HA - NA combinftions in human – avian influenza A virus reassortants. // Arch. Virol. 141: 1091-1099 (1996).
  30. Kaverin N.V., Gambaryan A.S., Bovin N.V., Rudneva I.A., Shilov A.A., Khodova O.M., Varich N.L., Sinitsin B.V., Makarova N.V., Kropotkina E.A. Postreassortment changes in influenza A virus hemagglutinin restoring HA – NA functional match. // Virol. 244: 315-321 (1998).
  31. Castrucci M.R., Kawaoka Y. Biologic importance of neuraminidase stalk length in influenza A virus. // J. Virol. 67: 759-764 (1993).
  32. Mitnaul J., Matrosovich M.N, Castrucci M.R., Tuzikov A.B., Bovin N.V., Kobasa D., Kawaoka Y. Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A viruses. // J. Virol. 74: 6015-6020 (2000).
  33. Wagner R., Wolf T., Herwig A., Pleschka S., Klenk H.-D. Interdependence of hemagglutinin glycosylation and neuraminidase as regulators of influenza growth: a study by reverse genetics. // J. Virol. 74: 6316-6323 (2000).
  34. Hughes M., Matrosovich M., Rodges M., Mc-regor M., Kawaoka Y. Influenza A viruses lacking sialidase activity can undergo multiple cycles of replication in cell culture, eggs, or mice. // J. Virol. 74: 5206-5212 (2000).
  35. Potier M., Mameli L., Belisle M., Dallaire L., Melancon S.B. Fluorometric assay with a sodium (4-methylumbelliferyl-α-D-N-acetylneuraminate) substrate. // Anal. Biochem.: 287-296 (1979).
  36. Engstler M., Talhouk J.W., Smith R.E., Schauer R. Chemical synthesis of 4-trifluoro methylumbelliferyl-α-D-N-acetylneuraminic acid glycoside and its use for the fluorometric detection of poorly expressed natural and recombinant sialidases. // Anal. Biochem. 250: 176-180 (1997).
  37. Buxton R.C., Edwards B., Juo R.R., Voyta J.C., Tisdale M., Bethell R.C. Development of a sensitive chemiluminescent neuraminidase assay for the determination of influenza virus susceptibility to zanamivir. // Anal. Biochem. 280: 291-300 (2000).
  38. Jourdian G.W., Dean L., Roselman S. A periodate-resortinol method for the quantitive estimation of five sialic acids and their glycosides. // J. Biol.Chem. 25: 430-435 (1971).
  39. Warren L. The thiobarbituric acid assay of sialic acids. // J. Biol. Chem. 234: 1971-1975 (1959).
  40. Lambre С.R., Terzidis H., Greffard A., Webster R.G. Measurement of anti-influenza neuraminidase antibody using a peroxidase-linked lectin and microtitre plates coated with natural substrates. // J. Immunol. Meth. 135: 49-57 (1990).
  41. Katinger D., Mochalova L., Chinarev A., Bovin N., Romanova J. Specificity of neuraminidase activity from influenza viruses isolated in different hosts tested with novel substrates. // Arch. Virol. 149: 2131-2140 (2004).
  42. Rudneva I.A., Kovaleva V.P., Varich N.L., Farashyan V.R., Gubareva L. V., Yamnikova S.S., Popova I.A., Presnova V.P., Kaverin N.V. Influenza A virus reassortants with surface glycoprotein genes of avian parent viruses: effects of HA and NA gene combinations on virus aggregation. // Arch. Virol. 133: 437-450 (1993).
  43. Couceiro J.N.S.S. Baum L.J. Characterization of the hemagglutinin receptor specificity and neuraminidase substrate specificity of clinical isolates of human influenza A viruses. // Mem. Inst. Oswaldo Cruz Rio de Janeiro 89: 587-591 (1994).
  44. Kobasa D., Kodihalli S., Luo M., Castrucci M.R., Donatelli I., Suzuki Y., Suzuki T., Kawaoka Y. Amino acid resides contributing to the substrate specificity of the influenza A virus neuraminidase. // J. Virol 73: 6743-6751 (1999).
  45. Baum L.G., Paulson J.C. The N2 neuraminidase of human influenza virus has acquired a substrate specificity complementary to the hemagglutinin receptor specificity. // Virol. 180: 10-15 (1991).
  46. Paulson J.C., Weinstein J., Dorland L., van Halbeek H., Viegenthart J.F.J. Newcastle disease virus contains a linkage-specific glycoprotein sialidase. // J. Biol. Chem. 257: 12734-12738 (1982).
  47. Mochalova, L.V., Korchagina E.Y., Kurova V.S., Shtyrya Y.A., Gambaryan A.S., Bovin N.V. Fluorescent assay for studying the substrate specificity of neuraminidase. //Anal. Biochem, 341, 190-193 (2005).
  48. Mochalova L., Kurova V., Shtyrya Y., Korchagina E., Gambaryan A., Belyanchikov I., Bovin N. Oligosaccharide specificity of influenza H1N1 virus neuraminidases. //Arch. Virol., 152, 2047-2057 (2007).
  49. Gambaryan A.S., Matrosovich M.N. A solid-phase enzyme-linked assay for influenza virus receptor-binding activity. //Journal of Virological Method's 39, 111-123(1992).
  50. Shtyrya Y.A., Mochalova L.V., Gambaryan A.S., Korchagina E.Y., Xu X., Klimov A.I., Bovin N.V. Neuraminidases of H9N2 influenza viruses isolated from different hosts display various substrate specificity. //Proceedings of international conference on options for the control of influenza VI. Canada, June 17-23, 2007. (M. Katz ed.), International Medical Press: 64-65 (2008).

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML
Скачать

© Shtyrya Y.A., Mochalova L.V., Bovin N.V., 2009

Creative Commons License
Эта статья доступна по лицензии Creative Commons Attribution 4.0 International License.

Данный сайт использует cookie-файлы

Продолжая использовать наш сайт, вы даете согласие на обработку файлов cookie, которые обеспечивают правильную работу сайта.

О куки-файлах