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Gene Review

LASVsSgp1  -  nucleoprotein

Lassa virus

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Disease relevance of LASVsSgp1

  • Comparison of full-length gene sequences for four Lassa virus strains representing the four lineages showed that the NP gene (up to 23.8% nucleotide difference and 12.0% amino acid difference) is more variable than the glycoprotein genes [1].
  • The arenavirus Lassa virus causes Lassa fever, a viral hemorrhagic fever that is endemic in the countries of Nigeria, Sierra Leone, Liberia, and Guinea and perhaps elsewhere in West Africa. To determine the degree of genetic diversity among Lassa virus strains, partial nucleoprotein (NP) gene sequences were obtained from 54 strains and analyzed [1].
  • The 5' and 3' terminal nucleotide sequences are conserved and complimentary for 19 nucleotides, the nucleoprotein and glycoprotein genes are arranged in ambisense coding strategy, and the intergenic region contains an inverted complimentary sequence, as do all other arenavirus S RNAs characterized to date [2].
  • Simultaneous expression of the Lassa virus N and GPC genes from a single recombinant vaccinia virus [3].
  • However, these mice developed fast-onset IDDM 14 days after LCMV infection, whereas single-transgenic RIP-NP littermates developed IDDM only within 4-5 months [4].

High impact information on LASVsSgp1

  • For these studies, double transgenic mice were generated that were genetically deficient in the production of IFN-gamma and express LCMV NP or GP in their beta cells [5].
  • To manipulate this CTL response, the viral NP gene was expressed in the thymus and peripheral T lymphocytes using the murine Thy1.2 promoter [6].
  • Strikingly, NP+/IFN-gamma+ mice spontaneously developed cytotoxic T lymphocyte activity on LCMV-infected targets and vaccinia virus-NP-infected ones without prior LCMV infection but NP+/IFN-gamma- mice did not, which indicates specific sensitization to the viral antigen by IFN-gamma [7].
  • Unexpectedly, we found that the expression of the lymphocytic choriomeningitis virus nucleoprotein only led to marginal enhancement of diabetes, although such NOD-nucleoprotein mice were not tolerant to nucleoprotein [8].
  • This system involves an LCMV minigenome and the minimal viral trans-acting factors (NP and L), expressed from separated cotransfected plasmids [9].

Chemical compound and disease context of LASVsSgp1


Biological context of LASVsSgp1

  • Suitable oligonucleotide primers and probes were synthesized to amplify Lassa virus (Josiah strain)-specific nucleoprotein and glycoprotein gene fragments by using reverse transcription combined with the polymerase chain reaction (PCR) [11].
  • First, we find that the relative recognition of the two LCMV proteins differs markedly on different H2 haplotypes; both proteins are seen on the H2bb background, while only NP is recognized on two other haplotypes (H2dd and H2qq) [12].
  • It is therefore proposed that this block in viral replication is brought about by a posttranslational effect on a viral gene product, probably the NP, present in reasonably large quantities both during homologous interference as well as persistent infection [13].
  • An ambisense MG coding for chloramphenicol acetyltransferase (CAT) and green fluorescent protein reporter genes instead of the nucleoprotein and glycoprotein open reading frames, respectively, served as a template for synthesis of full-length anti-MG (aMG) replicate and subgenomic size mRNA for reporter gene expression [14].
  • Comparison of the predicted amino acid sequences for NP and GP-C between the Armstrong CA-1371 strain and the WE strain shows over 90% amino acid identity [15].

Anatomical context of LASVsSgp1


Associations of LASVsSgp1 with chemical compounds


Regulatory relationships of LASVsSgp1


Analytical, diagnostic and therapeutic context of LASVsSgp1


  1. Genetic diversity among Lassa virus strains. Bowen, M.D., Rollin, P.E., Ksiazek, T.G., Hustad, H.L., Bausch, D.G., Demby, A.H., Bajani, M.D., Peters, C.J., Nichol, S.T. J. Virol. (2000) [Pubmed]
  2. Nucleotide sequence of the Lassa virus (Josiah strain) S genome RNA and amino acid sequence comparison of the N and GPC proteins to other arenaviruses. Auperin, D.D., McCormick, J.B. Virology (1989) [Pubmed]
  3. Simultaneous expression of the Lassa virus N and GPC genes from a single recombinant vaccinia virus. Morrison, H.G., Goldsmith, C.S., Regnery, H.L., Auperin, D.D. Virus Res. (1991) [Pubmed]
  4. Coexpression of B7-1 and viral ("self") transgenes in pancreatic beta cells can break peripheral ignorance and lead to spontaneous autoimmune diabetes. von Herrath, M.G., Guerder, S., Lewicki, H., Flavell, R.A., Oldstone, M.B. Immunity (1995) [Pubmed]
  5. Interferon-gamma is essential for destruction of beta cells and development of insulin-dependent diabetes mellitus. von Herrath, M.G., Oldstone, M.B. J. Exp. Med. (1997) [Pubmed]
  6. Thymic selection and adaptability of cytotoxic T lymphocyte responses in transgenic mice expressing a viral protein in the thymus. von Herrath, M.G., Dockter, J., Nerenberg, M., Gairin, J.E., Oldstone, M.B. J. Exp. Med. (1994) [Pubmed]
  7. Sensitization to self (virus) antigen by in situ expression of murine interferon-gamma. Lee, M.S., von Herrath, M., Reiser, H., Oldstone, M.B., Sarvetnick, N. J. Clin. Invest. (1995) [Pubmed]
  8. Minimal Impact of a De Novo-Expressed {beta}-Cell Autoantigen on Spontaneous Diabetes Development in NOD Mice. Martinic, M.M., Juedes, A.E., Bresson, D., Homann, D., Skak, K., Huber, C., Ling, E., Ejrnaes, M., Wolfe, T., Togher, L., Christen, U., von Herrath, M.G. Diabetes (2007) [Pubmed]
  9. RING finger Z protein of lymphocytic choriomeningitis virus (LCMV) inhibits transcription and RNA replication of an LCMV S-segment minigenome. Cornu, T.I., de la Torre, J.C. J. Virol. (2001) [Pubmed]
  10. Complete sequence of the S RNA of lymphocytic choriomeningitis virus (WE strain) compared to that of Pichinde arenavirus. Romanowski, V., Matsuura, Y., Bishop, D.H. Virus Res. (1985) [Pubmed]
  11. Detection of Lassa virus RNA in specimens from patients with Lassa fever by using the polymerase chain reaction. Lunkenheimer, K., Hufert, F.T., Schmitz, H. J. Clin. Microbiol. (1990) [Pubmed]
  12. Analyses of the cytotoxic T lymphocyte responses to glycoprotein and nucleoprotein components of lymphocytic choriomeningitis virus. Whitton, J.L., Southern, P.J., Oldstone, M.B. Virology (1988) [Pubmed]
  13. Homologous interference of lymphocytic choriomeningitis virus involves a ribavirin-susceptible block in virus replication. Géssner, A., Lother, H. J. Virol. (1989) [Pubmed]
  14. Dual role of the lymphocytic choriomeningitis virus intergenic region in transcription termination and virus propagation. Pinschewer, D.D., Perez, M., de la Torre, J.C. J. Virol. (2005) [Pubmed]
  15. Molecular characterization of the genomic S RNA segment from lymphocytic choriomeningitis virus. Southern, P.J., Singh, M.K., Riviere, Y., Jacoby, D.R., Buchmeier, M.J., Oldstone, M.B. Virology (1987) [Pubmed]
  16. Presentation of endogenous viral proteins in association with major histocompatibility complex class II: on the role of intracellular compartmentalization, invariant chain and the TAP transporter system. Oxenius, A., Bachmann, M.F., Ashton-Rickardt, P.G., Tonegawa, S., Zinkernagel, R.M., Hengartner, H. Eur. J. Immunol. (1995) [Pubmed]
  17. Anti-viral protection and prevention of lymphocytic choriomeningitis or of the local footpad swelling reaction in mice by immunization with vaccinia-recombinant virus expressing LCMV-WE nucleoprotein or glycoprotein. Hany, M., Oehen, S., Schulz, M., Hengartner, H., Mackett, M., Bishop, D.H., Overton, H., Zinkernagel, R.M. Eur. J. Immunol. (1989) [Pubmed]
  18. Viral infection of transgenic mice expressing a viral protein in oligodendrocytes leads to chronic central nervous system autoimmune disease. Evans, C.F., Horwitz, M.S., Hobbs, M.V., Oldstone, M.B. J. Exp. Med. (1996) [Pubmed]
  19. T cell-dependent IFN-gamma exerts an antiviral effect in the central nervous system but not in peripheral solid organs. Kündig, T.M., Hengartner, H., Zinkernagel, R.M. J. Immunol. (1993) [Pubmed]
  20. Novel LCMV-specific H-2k restricted CTL clones recognize internal viral gene products and cause CNS disease. Lewicki, H., McKee, T.A., Tishon, A., Salvato, M., Whitton, J.L., Oldstone, M.B. J. Neuroimmunol. (1992) [Pubmed]
  21. Reverse ELISA for IgG and IgM antibodies to detect Lassa virus infections in Africa. Emmerich, P., Thome-Bolduan, C., Drosten, C., Gunther, S., Ban, E., Sawinsky, I., Schmitz, H. J. Clin. Virol. (2006) [Pubmed]
  22. Enzyme-linked immunosorbent assay for detection of antibody to lymphocytic choriomeningitis virus in mouse sera, with recombinant nucleoprotein as antigen. Homberger, F.R., Romano, T.P., Seiler, P., Hansen, G.M., Smith, A.L. Lab. Anim. Sci. (1995) [Pubmed]
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