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MeSH Review

Lymphocytic Choriomeningitis Virus

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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].

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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


Anatomical context of Lymphocytic Choriomeningitis Virus


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


  1. Evidence for a differential avidity model of T cell selection in the thymus. Ashton-Rickardt, P.G., Bandeira, A., Delaney, J.R., Van Kaer, L., Pircher, H.P., Zinkernagel, R.M., Tonegawa, S. Cell (1994) [Pubmed]
  2. Serine protease inhibitor 6 protects cytotoxic T cells from self-inflicted injury by ensuring the integrity of cytotoxic granules. Zhang, M., Park, S.M., Wang, Y., Shah, R., Liu, N., Murmann, A.E., Wang, C.R., Peter, M.E., Ashton-Rickardt, P.G. Immunity (2006) [Pubmed]
  3. Requirements for bone marrow-derived antigen-presenting cells in priming cytotoxic T cell responses to intracellular pathogens. Lenz, L.L., Butz, E.A., Bevan, M.J. J. Exp. Med. (2000) [Pubmed]
  4. 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]
  5. Viruses as therapeutic agents. II. Viral reassortants map prevention of insulin-dependent diabetes mellitus to the small RNA of lymphocytic choriomeningitis virus. Oldstone, M.B., Ahmed, R., Salvato, M. J. Exp. Med. (1990) [Pubmed]
  6. Lymphocytic choriomeningitis virus: reemerging central nervous system pathogen. Barton, L.L., Hyndman, N.J. Pediatrics (2000) [Pubmed]
  7. Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice. Ohashi, P.S., Oehen, S., Buerki, K., Pircher, H., Ohashi, C.T., Odermatt, B., Malissen, B., Zinkernagel, R.M., Hengartner, H. Cell (1991) [Pubmed]
  8. Role of ISG15 protease UBP43 (USP18) in innate immunity to viral infection. Ritchie, K.J., Hahn, C.S., Kim, K.I., Yan, M., Rosario, D., Li, L., de la Torre, J.C., Zhang, D.E. Nat. Med. (2004) [Pubmed]
  9. Identification of alpha-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus. Cao, W., Henry, M.D., Borrow, P., Yamada, H., Elder, J.H., Ravkov, E.V., Nichol, S.T., Compans, R.W., Campbell, K.P., Oldstone, M.B. Science (1998) [Pubmed]
  10. LCMV-specific, class II-restricted cytotoxic T cells in beta 2-microglobulin-deficient mice. Muller, D., Koller, B.H., Whitton, J.L., LaPan, K.E., Brigman, K.K., Frelinger, J.A. Science (1992) [Pubmed]
  11. Self antigens expressed by solid tumors Do not efficiently stimulate naive or activated T cells: implications for immunotherapy. Speiser, D.E., Miranda, R., Zakarian, A., Bachmann, M.F., McKall-Faienza, K., Odermatt, B., Hanahan, D., Zinkernagel, R.M., Ohashi, P.S. J. Exp. Med. (1997) [Pubmed]
  12. Nitric oxide inhibits hepatitis B virus replication in the livers of transgenic mice. Guidotti, L.G., McClary, H., Loudis, J.M., Chisari, F.V. J. Exp. Med. (2000) [Pubmed]
  13. Interferon-alpha/beta inhibition of interleukin 12 and interferon-gamma production in vitro and endogenously during viral infection. Cousens, L.P., Orange, J.S., Su, H.C., Biron, C.A. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  14. The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies. Perez, M., Craven, R.C., de la Torre, J.C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  15. Hypergammaglobulinemia and autoantibody induction mechanisms in viral infections. Hunziker, L., Recher, M., Macpherson, A.J., Ciurea, A., Freigang, S., Hengartner, H., Zinkernagel, R.M. Nat. Immunol. (2003) [Pubmed]
  16. c-Jun NH(2)-terminal kinase (JNK)1 and JNK2 signaling pathways have divergent roles in CD8(+) T cell-mediated antiviral immunity. Arbour, N., Naniche, D., Homann, D., Davis, R.J., Flavell, R.A., Oldstone, M.B. J. Exp. Med. (2002) [Pubmed]
  17. Virus-induced transient bone marrow aplasia: major role of interferon-alpha/beta during acute infection with the noncytopathic lymphocytic choriomeningitis virus. Binder, D., Fehr, J., Hengartner, H., Zinkernagel, R.M. J. Exp. Med. (1997) [Pubmed]
  18. Pancreatic islet production of murine interleukin-10 does not inhibit immune-mediated tissue destruction. Lee, M.S., Wogensen, L., Shizuru, J., Oldstone, M.B., Sarvetnick, N. J. Clin. Invest. (1994) [Pubmed]
  19. Molecular analysis of the interaction of LCMV with its cellular receptor [alpha]-dystroglycan. Kunz, S., Sevilla, N., McGavern, D.B., Campbell, K.P., Oldstone, M.B. J. Cell Biol. (2001) [Pubmed]
  20. In vivo expression of perforin by CD8+ lymphocytes during an acute viral infection. Young, L.H., Klavinskis, L.S., Oldstone, M.B., Young, J.D. J. Exp. Med. (1989) [Pubmed]
  21. Aplastic anemia rescued by exhaustion of cytokine-secreting CD8+ T cells in persistent infection with lymphocytic choriomeningitis virus. Binder, D., van den Broek, M.F., Kägi, D., Bluethmann, H., Fehr, J., Hengartner, H., Zinkernagel, R.M. J. Exp. Med. (1998) [Pubmed]
  22. FTY720 immunosuppression impairs effector T cell peripheral homing without affecting induction, expansion, and memory. Pinschewer, D.D., Ochsenbein, A.F., Odermatt, B., Brinkmann, V., Hengartner, H., Zinkernagel, R.M. J. Immunol. (2000) [Pubmed]
  23. Purification and target cell range of in vivo elicited blast natural killer cells. Biron, C.A., Pedersen, K.F., Welsh, R.M. J. Immunol. (1986) [Pubmed]
  24. Aberrant T cells in beige mutant mice. Biron, C.A., Pedersen, K.F., Welsh, R.M. J. Immunol. (1987) [Pubmed]
  25. Effect of chronic viral infection on epitope selection, cytokine production, and surface phenotype of CD8 T cells and the role of IFN-gamma receptor in immune regulation. Tewari, K., Sacha, J., Gao, X., Suresh, M. J. Immunol. (2004) [Pubmed]
  26. A role for perforin in downregulating T-cell responses during chronic viral infection. Matloubian, M., Suresh, M., Glass, A., Galvan, M., Chow, K., Whitmire, J.K., Walsh, C.M., Clark, W.R., Ahmed, R. J. Virol. (1999) [Pubmed]
  27. T-lymphocyte downregulation after acute viral infection is not dependent on CD95 (Fas) receptor-ligand interactions. Lohman, B.L., Razvi, E.S., Welsh, R.M. J. Virol. (1996) [Pubmed]
  28. Chemokine gene expression in the brains of mice with lymphocytic choriomeningitis. Asensio, V.C., Campbell, I.L. J. Virol. (1997) [Pubmed]
  29. Mechanism of interleukin 12-mediated toxicities during experimental viral infections: role of tumor necrosis factor and glucocorticoids. Orange, J.S., Salazar-Mather, T.P., Opal, S.M., Spencer, R.L., Miller, A.H., McEwen, B.S., Biron, C.A. J. Exp. Med. (1995) [Pubmed]
  30. Major histocompatibility complex-linked susceptibility or resistance to disease caused by a noncytopathic virus varies with the disease parameter evaluated. Leist, T., Althage, A., Haenseler, E., Hengartner, H., Zinkernagel, R.M. J. Exp. Med. (1989) [Pubmed]
  31. 4-1BB costimulation is required for protective anti-viral immunity after peptide vaccination. Tan, J.T., Whitmire, J.K., Murali-Krishna, K., Ahmed, R., Altman, J.D., Mittler, R.S., Sette, A., Pearson, T.C., Larsen, C.P. J. Immunol. (2000) [Pubmed]
  32. Uncovering subdominant cytotoxic T-lymphocyte responses in lymphocytic choriomeningitis virus-infected BALB/c mice. van der Most, R.G., Concepcion, R.J., Oseroff, C., Alexander, J., Southwood, S., Sidney, J., Chesnut, R.W., Ahmed, R., Sette, A. J. Virol. (1997) [Pubmed]
  33. Neonatal DNA immunization with a plasmid encoding an internal viral protein is effective in the presence of maternal antibodies and protects against subsequent viral challenge. Hassett, D.E., Zhang, J., Whitton, J.L. J. Virol. (1997) [Pubmed]
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