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

• Previous studies have reported that the 3' half of the small, S, RNA species of the WE strain of lymphocytic choriomeningitis (LCM) virus codes for the viral nucleoprotein in a subgenomic, viral-complementary, mRNA species (Romanowski, V. and Bishop, D.H.L. (1985) Virus Res. 2, 35-51) [10].

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

• Furthermore, although the TAP molecules transport peptides of up to 15 amino acids in length, which potentially could bind to MHC class II molecules in the endoplasmic reticulum, such a process apparently does not occur for either the glycoprotein or the nucleoprotein [16].
• For example, B10.D2 H-2d mice generated measurable CTL responses only to Np; after immunization with a vaccinia-Np recombinant, LCMV titers were 10(4) times lower in spleens than in vaccinia-primed controls [17].
• To address this hypothesis, transgenic mice were generated that express the nucleoprotein or glycoprotein of lymphocytic choriomeningitis virus (LCMV) as self in oligodendrocytes [18].

Associations of LASVsSgp1 with chemical compounds

• Indirect immunofluorescence (IFA) of recombinant virus-infected cells demonstrated both the bright granular and diffuse patterns of staining characteristic of the Lassa nucleoprotein and glycoprotein, respectively [3].

Regulatory relationships of LASVsSgp1

• Mice were immunized with vesicular stomatitis virus (VSV) wild type (wt) and subsequently challenged with a mixture of two vaccinia recombinant viruses, one expressing the nucleoprotein of VSV (vacc-VSV-NP) the other expressing the glycoprotein of lymphocytic choriomeningitis virus (vacc-LCMV-GP) [19].

Analytical, diagnostic and therapeutic context of LASVsSgp1

• Vaccination with vaccinia-Np or Gp recombinants protected mice against lethal T cell-mediated lymphocytic choriomeningitis induced by LCMV or prevented the local footpad swelling reaction; these in vivo effects were H-2 dependent and followed the identical roles established for CTL recognition in vitro [17].
• Two other clones recognized the viral nucleoprotein, amino acids 93-100, as determined by protein deletion and peptide mapping studies [20].
• In both assays a tissue culture antigen was used in combination with a labeled anti-Lassa monoclonal antibody (Hufert FT, Ludke W, Schmitz H. Epitope mapping of the Lassa virus nucleoprotein using monoclonal anti-nucleocapsid antibodies. Arch Virol 1989;106(3-4):201-12) [21].
• Enzyme-linked immunosorbent assay for detection of antibody to lymphocytic choriomeningitis virus in mouse sera, with recombinant nucleoprotein as antigen [22].

References