Disease relevance of LCMVsSgp2

• However, we found that the generation of CTLs to one LCMV epitope (LCMV nucleoprotein 396-404) was dependent on BM-derived pAPCs but, surprisingly, TAP independent [1].
• Induction in vivo of antiviral cytotoxic T cell response was achieved in a MHC class I-dependent fashion by immunizing mice three times with a free unmodified 15-mer peptide derived from the nucleoprotein of lymphocytic choriomeningitis virus in IFA [2].
• Cytotoxic T cell (CTL) memory was analyzed after infection with lymphocytic choriomeningitis virus (LCMV) and recombinant Listeria monocytogenes (rLM) expressing the complete nucleoprotein of LCMV (rLM-NP(actA)) or only the immunodominant epitope of H-2(d) mice (rLM-NP(118-126)) [3].
• In the present study, we investigated the potential ability of an invasive adenylate cyclase toxin from Bordetella pertussis, carrying a CD8+ T cell epitope from the nucleoprotein of lymphocytic choriomeningitis virus (LCMV), to stimulate protective anti-viral immunity [4].
• 5) Vesicular stomatitis virus (VSV)-primed mutant mice could not eliminate nucleoprotein of VSV recombinant vaccinia virus upon intracerebral infection [5].

High impact information on LCMVsSgp2

• Infection of chimeric mice with either Listeria monocytogenes or vaccinia virus expressing the nucleoprotein (NP) antigen from lymphocytic choriomeningitis virus (LCMV) primed H2-D(b)-restricted, but not H2-K(d)-restricted CTL responses, demonstrating the requirement for BM-derived APCs for successful priming of CTL responses to these pathogens [6].
• LCMV infection of HY-transgenic C57BL/6 mice induced antiviral CTLs that lysed target cells coated with two of the three immunodominant epitopes previously defined for LCMV (glycoprotein 33 and nucleoprotein 397) [7].
• Such mice express the viral nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) under control of the rat insulin promoter in their pancreatic beta cells and < 2% spontaneously develop diabetes [8].
• The participation of IL-2 in insulin-dependent (type 1) diabetes (IDDM) was analyzed in transgenic (tg) mice expressing the nucleoprotein (NP) of lymphocytic choriomeningitis virus and IL-2 under control of the rat insulin promoter focally in beta cells of the islets of Langerhans [9].
• Neither cytotoxic T lymphocytes (CTL) nor antibodies directed against the viral tg (NP) were generated [9].

Chemical compound and disease context of LCMVsSgp2

• The nucleoprotein of Lassa virus, strain Josiah, was expressed in Escherichia coli as an N-terminally truncated, histidine-tagged recombinant protein [10].
• Foreign B and T cell epitopes inserted between the two halves of cLVG correspond to the B cell C3 neutralisation epitope of poliovirus VP1 protein and to the H2d CMH I restricted T cell epitope of the nucleoprotein of the lymphocytic choriomeningitis virus (LCMV) [11].

Biological context of LCMVsSgp2

• In this model, a LCMV polypeptide (either glycoprotein or nucleoprotein) expressed as a transgene in the islets is a target for autoimmune destruction of beta cells after LCMV infection [12].
• Anti-viral CTL were induced in vitro using a particle bombardment device or "gene-gun" to deliver plasmid DNA encoding the nucleoprotein of the lymphocytic choriomeningitis virus (LCMV) [13].
• Cross-presentation of the long-lived lymphocytic choriomeningitis virus nucleoprotein does not require neosynthesis and is enhanced via heat shock proteins [14].
• The LCMV NP contains the immunodominant CTL epitope (amino acids 118 to 126) recognized by mice of the H-2d haplotype [15].
• After LCMV infection, specific antibody responses against LCMV nucleoprotein were reduced four- to eightfold [16].

Anatomical context of LCMVsSgp2

• Indeed, disease incidence after viral (lymphocytic choriomeningitis virus [LCMV]) infection was reduced by approximately 30%, which was associated with a decrease of autoaggressive CD8 NP-specific lymphocytes in islets and pancreatic draining lymph nodes [17].
• In contrast, LCMV glycoprotein-specific TCR transgenic mice exhibited a drastically reduced ability to provide help for the generation of antibody responses specific for the virus-internal nucleoprotein, indicating that intramolecular/intrastructural help is limited to antigens that are accessible to B cells on the viral surface [18].
• NP was also detected in the cerebrospinal fluid of mice suffering from CD8+ T cell-mediated lymphocytic choriomeningitis after intracerebral infection [19].
• The LCMV nucleoprotein gene was inserted in phase with the sequence coding for the putative signal sequence of the hemolysin of L. monocytogenes in order to target its secretion into the cytosol of the infected cell [20].
• Of a total of 17 monoclonal antibodies (MAb) directed against structural proteins of the lymphocytic choriomeningitis (LCM) virus, 3 were specific for the viral nucleoprotein (p63) and attached to the plasma membrane of infected cells, as disclosed by the indirect immunofluorescence procedure and complement-mediated cytolysis [21].

Associations of LCMVsSgp2 with chemical compounds

• Two days after nucleoprotein biosynthesis was terminated in a tetracycline-regulated transfectant, the presentation of the NP118 epitope ceased [22].
• Cytoplasmic viral nucleoprotein complexes were labeled with [3H]uridine in the presence or absence of actinomycin D, purified partially by sedimentation in D2O-sucrose gradients, and adsorbed to fixed Staphylococus aureus cells in the presence of anti-LCMV immunoglobulin G [23].
• Lysosomotropic weak bases (chloroquine and ammonium chloride) and carboxylic ionophores (monensin and nigericin) inhibited virus entry, assessed as virus nucleoprotein expression at early times post-infection, indicating that the entry process involved a pH-dependent fusion step in intracellular vesicles [24].

Analytical, diagnostic and therapeutic context of LCMVsSgp2

• A specific antiviral cytotoxic immune response in vivo could be induced by the subcutaneous injection of the T-cell epitope of the lymphocytic choriomeningitis virus (LCMV) nucleoprotein as an unmodified free synthetic peptide (Arg-Pro-Gln-Ala-Ser-Gly-Val-Tyr-Met-Gly-Asn-Leu-Thr-Ala-Gln) emulsified in incomplete Freund's adjuvant [25].
• Using recombinant L. monocytogenes (rLM) strains expressing the full-length nucleoprotein (NP) or a single cytotoxic T-lymphocyte (CTL) epitope from lymphocytic choriomeningitis virus (LCMV), we analyzed antiviral CTL responses induced by rLM vaccination [26].
• We show that native NP is very stable in cell culture, while the ubiquitinated product is so rapidly degraded that it is barely detectable [27].
• We have previously shown that intramuscular injection of plasmid DNA encoding the nucleoprotein (NP) gene of lymphocytic choriomeningitis virus (LCMV) is capable of inducing immune responses and protecting 50% of adult mice against lethal and sublethal challenge with LCMV [28].
• Z protein and NP were expressed in Escherichia coli, affinity-purified, and used as antigen in Western blot [29].

References