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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

NP  -  nucleoprotein

Influenza B virus

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Disease relevance of NP

  • Comparison with the only other known sequence of an influenza B virus nucleoprotein gene (B/Singapore/222/79) indicates striking homology [1].
  • Like its influenza A virus counterpart, the influenza B/Lee/40 nucleoprotein is a basic protein with a relatively even distribution of its charged residues [1].
  • Monoclonal antibodies against influenza virus PB2 and NP polypeptides interfere with the initiation step of viral mRNA synthesis in vitro [2].
  • The results suggest the presence of phenotypically mixed nucleocapsids in the cells doubly infected with influenza A and B viruses; in the course of the virion formation, the nucleocapsids lacking the heterologous NP protein are selected [3].
  • The structural homology suggests functional similarity between the NP of influenza A and B viruses [4].

High impact information on NP

  • Low frequency of T cells directed to other influenza epitopes, including DRA1*0101/DRB1*0401-restricted matrix protein 60-73, DRA1*0101/DRB1*0101-restricted matrix protein 18-29, DRA1*0101/DRB1*0701-restricted HA 232-244 and DRA1*0101/DRB1*0101-restricted nucleoprotein 206-217 were also determined [5].
  • A detailed mutational analysis revealed that a combination of two sites in NP (A114 and H410) and one in PA (M431) controlled expression of ts, whereas these same changes plus two additional residues in M1 (Q159 and V183) controlled the att phenotype [6].
  • Phylogenetic profiles of the genes coding for the hemagglutinin (HA) protein, nucleoprotein (NP), matrix (M) protein, and nonstructural (NS) proteins of influenza B viruses isolated from 1940 to 1998 were analyzed in a parallel manner in order to understand the evolutionary mechanisms of these viruses [7].
  • Although evolutionary rates of the HA, NP, M, and NS genes of influenza B viruses were estimated to be generally lower than those of human influenza A viruses, genes of influenza B viruses demonstrated complex phylogenetic patterns, indicating alternative mechanisms for generation of virus variability [7].
  • The results obtained showed that MAbs to the PB2 and NP polypeptides interfered with the initiation step of mRNA-primed transcription [2].

Chemical compound and disease context of NP

  • The major virus-specific proteins (HA, NA, NP, NS1 and M) of five different isolates of influenza B virus (B/Lee/40, B/Osaka/2/70, B/Yamagata/1/73, B/Aomori/1/76 and B/Yamagata/26/77) were compared by limited proteolysis with Staphylococcus aureus V8 protease and subsequent polyacrylamide gel electrophoresis [8].

Biological context of NP


Anatomical context of NP

  • The remarkable conservation of nucleoprotein primary structure over a 39-year period probably reflects both selection for performance of specific functions and protection from antigenic selection by the host immune system [1].
  • Furthermore, B10.A(5R) mice that are non-responders for NP-specific class I killer cells could also be protected by immunization with rNP [11].
  • Viral propagation did not occur in liver or brain, but viral hemagglutinin, neuraminidase, and probably nucleoprotein antigens were produced in hepatocytes [12].
  • Samples of hybridoma cultures were incubated for 1 h with purified nucleoprotein preparation in microtiter wells precoated with rabbit anti-influenza A or B immunoglobulin, followed by washing and addition of anti-mouse HRPO-conjugate [13].
  • Among 20 stable cloned hybrid cells secreting monoclonal antibodies, one was specific for the nucleoprotein (NP), 11 were specific for the membrane (M) protein and eight were specific for the hemagglutinin (HA) [9].

Associations of NP with chemical compounds

  • Phenotypically mixed virus yields, obtained by coinfection of MDCK cells with influenza A/WSN/33 and B/Lee/40 viruses, contained both A/WSN/33 and B/Lee/40 NP proteins, as revealed by polyacrylamide gel electrophoresis of the purified 14C-amino acids-labeled virus [3].
  • Coexpression of NP and the P proteins in 293 cells was found to permit the expression and replication of a transfected model RNA based on segment 4 of B/Maryland/59, in which the hemagglutinin-coding region was replaced by a chloramphenicol acetyltransferase gene [14].
  • The commonly used concentration of 0.05% (v/v) Tween-20, when included in blocking and incubation buffers, greatly reduced the amount of detectable matrix protein but caused no detectable loss of HA and neuraminidase/nucleoprotein proteins [15].
  • The specificity of these antibodies for different epitopes of the nucleoprotein was demonstrated by competition experiments, using unlabelled and biotin-labelled purified antibodies in a sandwich assay [16].

Other interactions of NP

  • Comparative analysis of evolutionary mechanisms of the hemagglutinin and three internal protein genes of influenza B virus: multiple cocirculating lineages and frequent reassortment of the NP, M, and NS genes [7].
  • The nucleoproteins (NP) as well as the non-structural proteins (NS1) were also very similar among strains although the peptides of B/Lee/40 could be distinguished from those of the strains isolated from 1970 to 1977 [8].
  • HA and NA DNAs conferred complete protection against the lethal viral challenge, whereas NB and NP DNAs failed to provide protection against infection [17].

Analytical, diagnostic and therapeutic context of NP


  1. Influenza B virus genome: complete nucleotide sequence of the influenza B/lee/40 virus genome RNA segment 5 encoding the nucleoprotein and comparison with the B/Singapore/222/79 nucleoprotein. Briedis, D.J., Tobin, M. Virology (1984) [Pubmed]
  2. Monoclonal antibodies against influenza virus PB2 and NP polypeptides interfere with the initiation step of viral mRNA synthesis in vitro. Bárcena, J., Ochoa, M., de la Luna, S., Melero, J.A., Nieto, A., Ortín, J., Portela, A. J. Virol. (1994) [Pubmed]
  3. Virions and intracellular nucleocapsids produced during mixed heterotypic influenza infection of MDCK cells. Sklyanskaya, E.I., Varich, N.L., Amvrosieva, T.V., Kaverin, N.V. J. Virol. (1985) [Pubmed]
  4. Complete nucleotide sequence of the nucleoprotein gene of influenza B virus. Londo, D.R., Davis, A.R., Nayak, D.P. J. Virol. (1983) [Pubmed]
  5. HLA class II-restricted CD4+ T cell responses directed against influenza viral antigens postinfluenza vaccination. Danke, N.A., Kwok, W.W. J. Immunol. (2003) [Pubmed]
  6. Multiple gene segments control the temperature sensitivity and attenuation phenotypes of ca B/Ann Arbor/1/66. Hoffmann, E., Mahmood, K., Chen, Z., Yang, C.F., Spaete, J., Greenberg, H.B., Herlocher, M.L., Jin, H., Kemble, G. J. Virol. (2005) [Pubmed]
  7. Comparative analysis of evolutionary mechanisms of the hemagglutinin and three internal protein genes of influenza B virus: multiple cocirculating lineages and frequent reassortment of the NP, M, and NS genes. Lindstrom, S.E., Hiromoto, Y., Nishimura, H., Saito, T., Nerome, R., Nerome, K. J. Virol. (1999) [Pubmed]
  8. A comparison of proteins among various influenza B virus strains by one-dimensional peptide mapping. Nakamura, K., Kitame, F., Homma, M. J. Gen. Virol. (1981) [Pubmed]
  9. Hybridoma antibodies produced against bromelain derived cores of influenza virus. Lecomte, J. Microbiol. Immunol. (1985) [Pubmed]
  10. Long-lasting anti-viral cytotoxic T lymphocytes induced in vivo with chimeric-multirestricted lipopeptides. Sauzet, J.P., Déprez, B., Martinon, F., Guillet, J.G., Gras-Masse, H., Gomard, E. Vaccine (1995) [Pubmed]
  11. Anti-viral immunity induced by recombinant nucleoprotein of influenza A virus. II. Protection from influenza infection and mechanism of protection. Tite, J.P., Hughes-Jenkins, C., O'Callaghan, D., Dougan, G., Russell, S.M., Gao, X.M., Liew, F.Y. Immunology (1990) [Pubmed]
  12. Experimental influenza B virus toxicity in mice. A possible model for Reye's syndrome. Davis, L.E., Cole, L.L., Lockwood, S.J., Kornfeld, M. Lab. Invest. (1983) [Pubmed]
  13. One-incubation time-resolved fluoroimmunoassay based on monoclonal antibodies in detection of influenza A and B viruses directly in clinical specimens. Nikkari, S., Halonen, P., Kharitonenkov, I., Kivivirta, M., Khristova, M., Waris, M., Kendal, A. J. Virol. Methods (1989) [Pubmed]
  14. The N-terminal extension of the influenza B virus nucleoprotein is not required for nuclear accumulation or the expression and replication of a model RNA. Stevens, M.P., Barclay, W.S. J. Virol. (1998) [Pubmed]
  15. Western blot analysis of antibody responses to influenza virion proteins. Qiu, D., Tannock, G.A., Barry, R.D., Jackson, D.C. Immunol. Cell Biol. (1992) [Pubmed]
  16. Monoclonal antibodies for the rapid diagnosis of influenza-B virus infections by ELISA: production and characterization. Glikmann, G., Chen, S.N., Mordhorst, C.H., Koch, C. Clinical and diagnostic virology. (1995) [Pubmed]
  17. Protection against influenza B virus infection by immunization with DNA vaccines. Chen, Z., Kadowaki, S., Hagiwara, Y., Yoshikawa, T., Sata, T., Kurata, T., Tamura, S. Vaccine (2001) [Pubmed]
  18. Expression of influenza A and B virus nucleoprotein antigens in baculovirus. Rota, P.A., Black, R.A., De, B.K., Harmon, M.W., Kendal, A.P. J. Gen. Virol. (1990) [Pubmed]
  19. A rapid method for immunotitration of influenza viruses using flow cytometry. Lonsdale, R., Pau, M.G., Oerlemans, M., Ophorst, C., Vooys, A., Havenga, M., Goudsmit, J., UytdeHaag, F., Marzio, G. J. Virol. Methods (2003) [Pubmed]
  20. Rapid detection and identification of two lineages of influenza B strains with monoclonal antibodies. Nakagawa, N., Maeda, A., Kase, T., Kubota, R., Okuno, Y. J. Virol. Methods (1999) [Pubmed]
  21. Detection of type B influenza virus genes from biopsied gastric mucosa. Hayase, Y., Tobita, K., Sato, H. J. Gastroenterol. (2002) [Pubmed]
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