Disease relevance of Lymphocytic Choriomeningitis Virus

• Positive and negative selection of a lymphocytic choriomeningitis virus (LCMV) peptide-specific, H-2Db-restricted T cell clone (P14) was studied using TAP1- and TAP1+ mice transgenic for P14 T cell receptor (TCR) alpha and beta genes [1].
• Infection with either Lymphocytic Choriomeningitis virus (LCMV) or Listeria monocytogenes (LM) revealed increased apoptosis and diminished survival of Spi6 knockout (KO) CTLs, which was cell autonomous and could be corrected by GrB deficiency [2].
• 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 [3].
• (Kagi, D., B. Odermatt, P. Ohashi, R.M. Zinkernagel, and H. Hengartner, 1996, J. Exp. Med. 183:2143-2149) showed, using RIP LCMV perforin-deficient mice, that IDDM does not occur in the absence of perforin [4].
• Genetic reassortant viruses generated between the IDDM therapeutic strain of LCMV Pasteur and the nontherapeutic variant, LCMV Clone 13, were used to treat NOD mice [5].

Psychiatry related information on Lymphocytic Choriomeningitis Virus

• Congenital LCMV infection is a significant, often unrecognized cause of chorioretinitis, hydrocephalus, microcephaly or macrocephaly, and mental retardation [6].

High impact information on Lymphocytic Choriomeningitis Virus

• To address the mechanisms of tolerance to extrathymic proteins, we have generated transgenic mice expressing the lymphocytic choriomeningitis viral (LCMV) glycoprotein (GP) in the beta islet cells of the pancreas [7].
• Consistent with these findings, mouse embryonic fibroblasts (MEF) and bone marrow-derived macrophages from Usp18(-/-) mice showed restricted LCMV replication [8].
• Cells bearing a null mutation of the gene encoding DG were resistant to LCMV infection, and reconstitution of DG expression in null mutant cells restored susceptibility to LCMV infection [9].
• When beta 2M-/- mice were infected with LCMV, many died from LCMV disease and produced a specific response to LCMV mediated by CD4+ CTLs that were class II-restricted [10].
• Spi6 KO mice in turn were impaired in their ability to clear LCMV infection [2].

Chemical compound and disease context of Lymphocytic Choriomeningitis Virus

• Infection of transgenic mice with LCMV readily abolishes peripheral unresponsiveness to the self LCMV GP antigen, resulting in a CD8+ T cell-mediated diabetes [7].
• However, LCMV infection induced an antitumor CTL response which efficiently reduced the tumor mass, resulting in temporarily normalized blood glucose levels and prolonged survival of double transgenic RIP(GP x Tag2) mice (137 +/- 18 d) as opposed to control RIP-Tag2 mice (88 +/- 8 d) [11].
• Conversely, iNOS-deficient mice were not resistant to the antiviral effect of IFN-alpha/beta induced by either polyinosinic-polycytidylic acid complex or by lymphocytic choriomeningitis virus (LCMV) infection [12].
• Moreover, endogenous IFN-alpha/beta induced by LCMV inhibited in vivo lipopolysaccharide stimulation of IL-12 production [13].
• LCMV and LFV Z proteins contain proline-rich motifs that are characteristic of late domains [14].

Biological context of Lymphocytic Choriomeningitis Virus

• The process is dependent on help from CD4+ T cells that specifically recognize LCMV peptides presented by B cells on major histocompatibility complex class II molecules [15].
• However, JNK1(-/-) mice cleared LCMV infection with similar kinetics as JNK(+/+) mice [16].
• Thus, the reversible depression of hematopoiesis during early LCMV infection was not mediated by LCMV-WE-specific cytotoxic T lymphocyte, cytolysis, or secreted IFN-gamma from virally induced NK cells but was a direct effect of IFN-alpha/beta [17].
• After LCMV infection, IL-10 and LCMV antigen double transgenic mice developed diabetes earlier than LCMV antigen single transgenic littermates, suggesting that IL-10 does not inhibit islet antigen presentation or recognition [18].
• This competition of the virus with ECM molecules for receptor binding likely explains the recently found correlation between the affinity of LCMV binding to alpha-DG, tissue tropism, and pathological potential [19].

Anatomical context of Lymphocytic Choriomeningitis Virus

• We were able to detect a large accumulation of perforin antigen in CD8+/Thy-1+/asialo GM1+/CD4- lymphocytes, which in fact represent the main infiltrating cell type found in brain and liver sections obtained during the late acute stage of LCMV infection [20].
• To evaluate the effects on hematopoiesis exerted by sustained viral replication in the presence of activated T cells, blood values and bone marrow (BM) function were analyzed in chronic infection with lymphocytic choriomeningitis virus (LCMV) in perforin-deficient (P0/0) mice [21].
• Oral FTY720 (0.3 mg/kg/day) did not affect LCMV replication and specific CTL and B cells were induced and expanded normally [22].
• Blast natural killer (NK) cells were elicited in the spleens of mice by treatments with the interferon inducers lymphocytic choriomeningitis virus (LCMV) or polyinosinic-polycytidylic acid (poly I:C) [23].
• Virus-specific, class I-restricted CTL activity mediated by total spleen leukocytes isolated from bg/+ or +/+ mice on days 7 or 9 postinfection with LCMV was moderately higher than that mediated by spleen cells isolated from bg/bg mice [24].

Gene context of Lymphocytic Choriomeningitis Virus

• Survival of Usp18(-/-) mice after intracerebral LCMV infection correlated with a severe inhibition of LCMV RNA replication and antigen expression in the brain and increased levels of protein ISGylation [8].
• Whereas expression of CD44 was minimally altered, a greater proportion of LCMV-specific memory CD8 T cells were CD62L(low) in mice that have recovered from a chronic LCMV infection, compared with acutely infected mice [25].
• Perforin-deficient (perf -/-) mice chronically infected with lymphocytic choriomeningitis virus (LCMV) contained greater numbers of antiviral T cells compared to persistently infected +/+ mice [26].
• Thus, CD95 is not required for the immune downregulation of the CD8+-T-lymphocyte response following acute LCMV infection [27].
• These findings demonstrate the expression of a number of chemokine genes in the brains of mice infected with LCMV [28].

Analytical, diagnostic and therapeutic context of Lymphocytic Choriomeningitis Virus

• Northern blot and in situ hybridization analyses demonstrated that IL-12 induced TNF-alpha expression and that LCMV infection synergized with IL-12 for induction of this factor [29].
• The influence of major transplantation antigens on susceptibility to T cell-mediated disease caused by infection with the noncytopathic virus lymphocytic choriomeningitis virus (LCMV) was evaluated in B10 H-2-congenic mice [30].
• These results show that immunization with a single LCMV peptide provides long term protection against LCMV infection and point to costimulatory molecules such as 4-1BB as important components for generating protective immunity after vaccination [31].
• Analysis of a panel of Kd binding LCMV peptides revealed that residues 283 to 291 from the viral glycoprotein (GP(283-291)) comprise a major new epitope in the adoptive transfer model [32].
• 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 [33].

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