Molecular Biology of the Prototype Arenavirus, Lymphocytic Choriomeningitis Virus

  • Maria S. Salvato
Part of the The Viruses book series (VIRS)


Structural analysis of a well-characterized virus such as lymphocytic choriomeningitis virus (LCMV) is of particular importance in interpret-ing complex biological phenomena. Complete determination of the nu-cleotide sequence of LCMV establishes the structural features and cod-ing capacity of the virus genome. It enables further studies on the gene expression and replication mechanisms of arenaviruses, with potential significance for our understanding of viral persistence and pathogenesis.


Genomic Segment Nucleocapsid Protein Single Amino Acid Change Lymphocytic Choriomeningitis Lymphocytic Choriomeningitis Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ahmed, R., Simon, R., Matloubian, M., Kolhekar, S., Southern, P., and Freedman, D., 1988, Genetic analysis of immunosuppressive viral variants causing chronic infection: Importance of mutation in the L RNA segment of lymphocytic choriomeningitis virus, J.. Virol. 62:3301.PubMedGoogle Scholar
  2. Auperin, D. D., Compans, R. W., and Bishop, D. H. L, 1982, Nucleotide sequence conservation at the 3’ termini of the virion RNA species of New World and Old World arenaviruses, Virology 121:200.PubMedCrossRefGoogle Scholar
  3. Auperin, D. D., Romanowski, V., Galinski, M., and Bishop, D. H. L, 1984, Sequence studies of Pichinde arenavirus S RNA indicate a novel coding strategy, ambisense viral S RNA, J. Virol. 52:897.PubMedGoogle Scholar
  4. Bass, B. L., and Weintraub, H., 1988, An unwinding activity that covalently modifies its double-stranded RNA substrate, Cell 55:1089.PubMedCrossRefGoogle Scholar
  5. Bellocq, C., Raju, R., Patterson, J., and Kolakofsky, D., 1987, Translational requirement of La Cross Virus S-mRNA synthesis: In vitro studies, J. Virol. 61:87.PubMedGoogle Scholar
  6. Bishop, D. H. L., and Auperin, D. D., 1987, Arenavirus gene structure and organization, Curr. Top. Microbiol. Immunol. 133:5–17.PubMedCrossRefGoogle Scholar
  7. Boersma, D. P., and Compans, R. W., 1985, Synthesis of Tacaribe virus polypeptides in an in vitro coupled transcription and translation system, Virus Res. 2:261.PubMedCrossRefGoogle Scholar
  8. Buchmeier, M. J., and Parekh, B. S., 1987, Protein structure and expression among arena-viruses, Curr. Top. Microbiol. Immunol. 133:41.PubMedCrossRefGoogle Scholar
  9. Cattaneo, R., Schmid, A., Eschle, D., Baczko, K., ter Meulen, V., and Billeter, M. A., 1988, Biased hypermutation and other genetic changes in defective measles viruses in human brain infections, Cell 55:255.PubMedCrossRefGoogle Scholar
  10. Dahlberg, J. E., Obijeski, J. F., and Korb, J., 1977, Electron microscopy of the segmented RNA genome of La Crosse virus: Absense of circular molecules, J. Virol. 22:203.PubMedGoogle Scholar
  11. DePolo, N. J., Giachetti, C., and Holland, J. J., 1987, Continuing co-evolution of virus and defective interfering particles and of viral genome sequences during undiluted passages: virus mutants exhibiting nearly complete resistance to formerly dominant defective interfering particles, J. Virol. 61:454.Google Scholar
  12. Donahue, T. F., Cigan, A. M., Pabich, E. K., and Valavicius, B. C., 1988, Mutations at a Zn(II) finger motif in the yeast eIF-2ß gene alter ribosomal start-site selection during the scanning process, Cell 54:621.PubMedCrossRefGoogle Scholar
  13. Dreher, T. W., Bujarski, J. J., and Hall, T. C., 1984, Mutant viral RNAs synthesized in vitro show altered aminoacylation and replicase template activities,Nature 311:171.PubMedCrossRefGoogle Scholar
  14. Dreyfuss, G., Swanson, M. S., and Pinol-Roma, S., 1988, Heterogeneous nuclear ribonu-cleoprotein particles and the pathway of mRNA formation, TIBS 13:86.PubMedGoogle Scholar
  15. Edery, I., Petryshyn, R., and Sonenberg, N., 1989, Activation of double-stranded RNA-dependent kinase (ds1) by the TAR region of HIV-1 mRNA: A novel translational control mechanism, Cell 56:303.PubMedCrossRefGoogle Scholar
  16. Farrell, P. J., Balkow, K., Hunt, T., Jackson, R. J., and Trachsel, H., 1977, Phosphorylation of initiation factor eIF-2 and the control of reticulocyte protein synthesis, Cell 11:187.PubMedCrossRefGoogle Scholar
  17. Fields, B. N., and Green, M. I., 1982, Genetic and molecular mechanisms of viral pathogen-esis: implications for prevention and treatment, Nature (London) 300:19.CrossRefGoogle Scholar
  18. Francis, S. J., and Southern, P. J., 1988, Deleted viral RNAs and lymphocytic choriomenin-gitis virus persistence in vitro, J. Gen. Virol. 69:1893.PubMedCrossRefGoogle Scholar
  19. Fuller-Pace, F., and Southern, P. J., 1988, Temporal analysis of transcription and replication during acute infection with lymphocytic choriomeningitis virus, Virology 162:260.PubMedCrossRefGoogle Scholar
  20. Holland, J., Spindler, K., Horodyski, F., Grabau, E., Nichol, S., and Vanderpol, S., 1982, Rapid evolution of RNA genomes, Science 215:1577.PubMedCrossRefGoogle Scholar
  21. Howard, C. R., and Buchmeier, M. J., 1983, A protein kinase activity in lymphocytic choriomeningitis virus and identification of the phosphorylated product using monoclonal antibody, Virology 126:538.PubMedCrossRefGoogle Scholar
  22. Hsu, M-T., Parvin, J. D., Gupta, S., Krystal, M., and Palese, P., 1987, Genomic RNAs of influenza virus are held in a circular conformation in virions and in infected cells by a terminal panhandle, Proc. Natl. Acad. Sci. 84:8140.PubMedCrossRefGoogle Scholar
  23. Jacobs, R. P., and Cole, G. A., 1976, Lymphocytic choriomeningitis induced immunosuppression: A virus-induced macrophage defect, J. Immunol. 117:1004.PubMedGoogle Scholar
  24. Joly, E., Salvato, M., Whitton, J. L., and Oldstone, M. B. A., 1989, Polymorphism of CTL clones that recognize a defined nine amino acid immunodominant domain on lymphocytic choriomeningitis virus glycoprotein, J. Virol. 63:1845.PubMedGoogle Scholar
  25. Kao, S., Calman, A., Luciw, P., and Peterland, B. M., 1987, Anti-termination of transcription within the long terminal repeat of HIV-I by tat gene product, Nature 330:489.PubMedCrossRefGoogle Scholar
  26. Keene, J. D., Schubert, M., and Lazzarini, R. A., 1979, Terminal sequences of vesicular stomatitis virus RNA are both complimentary and conserved, J. Virol. 32:167.PubMedGoogle Scholar
  27. Kirk, W., Cash, P., Peters, C. J., and Bishop, D. H. L., 1980, Formation and characterization of an intertypic lymphocytic choriomeningitis recombinant virus, J. Gen. Virol. 51:213.PubMedCrossRefGoogle Scholar
  28. Kitajewski, J., Schneider, R. J., Safer, B., Munemitsu, S. M., Samuel, C. E., Thimmappaya, B., and Shenk, T., 1986, Adenovirus VA1 RNA antagonizes the antiviral action of interferon by preventing activation of the interferon-induced eIF2a kinase, Cell 45:195.PubMedCrossRefGoogle Scholar
  29. Klavinskis, L. S., and Oldstone, M. B. A., 1987, Lymphocytic choriomeningitis virus can persistently infect thyroid epithelial cells and perturb thyroid hormone production, J. Gen. Virol. 68:1867.PubMedCrossRefGoogle Scholar
  30. Klug, A., and Rhodes D., 1987, ‘Zinc fingers’: A novel protein motif for nucleic acid recognition, Trends Biochem. Sci. 12:461.CrossRefGoogle Scholar
  31. Li, Y., Luo, L., Snyder, R. M., and Wagner, R. R., 1988, Expression of the M gene of vesicular stomatitis virus cloned in various vaccinia virus vectors, J. Virol. 62:776.PubMedGoogle Scholar
  32. Matloubian, M., Somasundaram, T., Kolhekar, S. R., Selvakumar, R., and Ahmed, R., 1990, Genetic basis of viral persistence: Single amino acid change in the viral glycoprotein affects ability of lymphocytic choriomeningitis virus to persist in adult mice, J. Exp. Med. 172:1043.PubMedCrossRefGoogle Scholar
  33. Miller, J., McLachlan, A. D., and Klug, A., 1985, Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes, EMBO J. 4:1609.PubMedGoogle Scholar
  34. Mitsutani, S., and Colonno, R. J., 1985, In vitro synthesis of an infectious RNA from cDNA clones of human rhinovirus type 14, J. Virol. 56:628.Google Scholar
  35. Moran, E., and Mathews, M. B., 1987, Multiple functional domains in the adenovirus E1A gene, Cell 48:177.PubMedCrossRefGoogle Scholar
  36. Nakajima, K., Ueda, M., and Sugiura, A., 1979, Origin of small RNA in von Magnus particles in influenza virus, J. Virol. 29:1142.PubMedGoogle Scholar
  37. Nelson, J. A., Gnann, J. W., and Ghazal, P., 1990, Regulation and tissue specific expression of human cytomegalovirus, Curr. Top. Microbiol. Immunol. 154:75.PubMedCrossRefGoogle Scholar
  38. Oldstone, M. B. A., and Dixon, F., 1970, Pathogenesis of chronic disease associated with persistent lymphocytic choriomeningitis virus. II. Relationship of anti-lymphocytic choriomeningitis immune response to tissue injury in chronic lymphocytic choriomeningitis disease, J. Exp. Med. 131:1.PubMedCrossRefGoogle Scholar
  39. Oldstone, M. B. A., Sinha, Y N, Blount, P., Tishon, A., Rodriguez, M., von Wedel, R., and Lampert, P. W., 1982, Virus induced alterations in homeostasis: Alterations in differentiated functions of infected cells in vivo, Science 218:1125.PubMedCrossRefGoogle Scholar
  40. Oldstone, M. B. A., Salvato, M., Tishon, A., and Lewicki, H., 1988, Virus—lymphocyte interactions. III. Biologic parameters of a virus variant that fails to generate CTL and establishes persistent infection in immunocompetent hosts, Virology 164:507.PubMedCrossRefGoogle Scholar
  41. Palmer, E. L., Obijeski, J. F., Webb, P. A., and Johnson, K. M., 1977, The circular segmented nucleocapsid of an Arenavirus, Tacaribe virus, J. Gen. Virol. 36:541.PubMedCrossRefGoogle Scholar
  42. Parker, R., Siliciano, P. G., and Guthrie, C., 1987, Recognition of the TACTAAC box during mRNA splicing in yeast involves base pairing to the U2-like snRNA, Cell 49:229.PubMedCrossRefGoogle Scholar
  43. Pathak, V. K., Nielson, P. J., Trachsel, H., and Hershey, J. W. B., 1988, Structure of the ß subunit of translation initiation factor eIF-2, Cell 54:633.PubMedCrossRefGoogle Scholar
  44. Porterfield, J. S., Casals, J., Chumakov, M. P., Gaidamovich, S. Y., Hannoun, C., Holmes, I. H., Horzinek, M. C., Mussgay, M., Okerblom, N., and Russell, P. K., 1975, Bunyaviruses and Bunyaviridae, Intervirology 6:13.PubMedCrossRefGoogle Scholar
  45. Puglisi, J. D., Wyatt, J. R., and Tinoco, I., 1988, A pseudonotted RNA oligonucleotide, Nature 331:283.PubMedCrossRefGoogle Scholar
  46. Racaniello, V. R., and Baltimore, D., 1981, Cloned poliovirus complementary DNA is infectious in mammalian cells, Science 214:916.PubMedCrossRefGoogle Scholar
  47. Raju, R., and Kolakofsky, D., 1987, Translational requirement of La Cross virus S-mRNA synthesis: In vivo studies, J. Virol. 61:96.PubMedGoogle Scholar
  48. Ransone, L. J., and Dasgupta, A., 1988, A heat-sensitive inhibitor in poliovirus-infected cells which selectively blocks phosphorylation of the a subunit of eukaryotic initiation factor 2 by the double-stranded RNA-activated protein kinase, J. Virol. 62:3551.PubMedGoogle Scholar
  49. Rice, C. M., Levis, R., Strauss, J. H., and Huang, H. V., 1987, Production of infectious RNA transcripts from Sindbis virus cDNA clones: Mapping of lethal mutations, rescue of a temperature-sensitive marker, and in vitro mutagenesis to generate defined mutants, J. Virol. 61:3809.PubMedGoogle Scholar
  50. Riviere, Y., 1987, Mapping arenavirus genes causing virulence, Curr. Top. Microbiol. Immunol. 133:59.PubMedCrossRefGoogle Scholar
  51. Riviere, Y., Ahmed, R., Southern, P. J., and Oldstone, M. B. A., 1985a, Perturbation of differentiated functions during viral infection in vivo: II. Viral reassortants map growth hormone defect at the S RNA of the lymphocytic choriomeningitis virus genome, Virology 142:175.CrossRefGoogle Scholar
  52. Riviere, Y., Ahmed, R., Southern, P. J., Buchmeier, M. J., and Oldstone, M. B. A., 1985b, Genetic mapping of lymphocytic choriomeningitis virus pathogenicity: Virulence in guinea pigs is associated with the L RNA segment, J. Virol. 55:704.Google Scholar
  53. Riviere, Y., Southern, P. J., Ahmed, R., and Oldstone, M. B. A., 1986, Biology of cloned cytotoxic T-lymphocytes specific for lymphocytic choriomeningitis virus. V. Recognition is restricted to gene products encoded by the viral S RNA segment, J. Immunol. 136:304.PubMedGoogle Scholar
  54. Rodriguez, M., von Wedel, R. J., Garrett, R. S., and Lampert, P. S., 1983, Pituitary dwarfism in mice persistently infected with LCMV, Lab. Invest. 49:48.PubMedGoogle Scholar
  55. Romanowski, V., Matsuura, Y., and Bishop, D. H. L., 1985, Complete sequence of the S RNA of lymphocytic choriomeningitis virus (WE strain) compared to that of Pichinde arenavirus, Virus Res. 3:101.PubMedCrossRefGoogle Scholar
  56. Salvato, M., 1989, Ambisense nature of the L genomic segment of LCMV, in: Genetics and Pathogenicity of Negative Strand Viruses (B. Mahy and D. Kolakofsky, eds.), pp. 168–174. Elsevier Press, New York, Amsterdam.Google Scholar
  57. Salvato, M. S., and Shimomaye, E. M., 1989, The completed sequence of LCMV reveals a unique RNA structure and a new gene for a zinc-finger protein, Virology 173:1.PubMedCrossRefGoogle Scholar
  58. Salvato, M. S., Shimomaye, E. M., Southern, P. J., and Oldstone, M. B. A., 1988, Virus, lymphocyte interactions. IV. Molecular characteristics of LCMV Armstrong (CTL+) small genomic segment and that of its variant, clone 13 (CTI-), Virology 164:517.PubMedCrossRefGoogle Scholar
  59. Salvato, M. S., Shimomaye, E. M., Schweighofer, K. S., and Oldstone, M. B. A., 1989a, Mapping genes of lymphocytic choriomeningitis virus which determine the cytotoxic T-lymphocyte response, in: Cell biology of virus entry, replication, and pathogenesis, UCLA Symp. Mol. Cell. Biol. 90:329.Google Scholar
  60. Salvato, M. S., Shimomaye, E. M., and Oldstone, M. B. A., 1989b, The primary structure of the lymphocytic choriomeningitis L gene encodes a putative RNA polymerase, Virology 169:377.CrossRefGoogle Scholar
  61. Salvato, M. S., Borrow, P., Shimomaye, E. M., and Oldstone, M. B. A., 1991, Molecular basis of viral persistence: as single amino acid change in the glycoprotein of lymphocytic choriomeningitis virus is associated with suppression of the antiviral cytotoxic T-lymphocyte response and establishment of persistence, J. Virol. 65:1863.PubMedGoogle Scholar
  62. Salvato, M. S., Schweighofer, K. J., Burns, J., Shimomaye, E. M., 1992, Biochemical and immunological evidence that the 11 kDa zinc-binding protein of lymphocytic choriomeningitis virus is a structural component of the virus, Virus Research 22:185.PubMedCrossRefGoogle Scholar
  63. Schiff, L. A., Nibert, M. L., Co, M. S., Brown, E. G., and Fields, B. N., 1988, Distinct binding sites for zinc and double-stranded RNA in the reovirus outer capsid protein sigma 3, Mol. Cell. Biol. 8:273.PubMedGoogle Scholar
  64. Shimomaye, E. M., and Salvato, M. S., 1989, Use of AMV reverse transcriptase at high temperature for sequence analysis of highly structured RNA, Gene Analysis Techniques 6:25.PubMedCrossRefGoogle Scholar
  65. Singh, M. K., Fuller-Pace, F. V., Buchmeier, M. J., and Southern, P. J., 1987, Analysis of the genomic L segment from lymphocytic choriomeningitis virus, Virology 161:448.PubMedCrossRefGoogle Scholar
  66. Southern, P. J., and Bishop, D. H. L., 1987, Sequence comparison among arenaviruses, Curr. Top. Microbiol. Immunol. 133:19–39.PubMedCrossRefGoogle Scholar
  67. Southern, P. J., Blount, P., and Oldstone, M. B. A., 1984, Analysis of persistent virus infections by in situ hybridization to whole-mouse sections, Nature 312:555.PubMedCrossRefGoogle Scholar
  68. Southern, P. J., Singh, M. K., Riviere, Y., Jacoby, D. R., Buchmeier, M. J., and Oldstone, M. B. A., 1987, Molecular characterization of the genomic S RNA segment from LCMV, Virology 157:145.PubMedCrossRefGoogle Scholar
  69. Strauss, E. G., and Strauss, J. H., 1983, Replication strategies of the single-stranded RNA viruses of eukaryotes, Curr. Top. Microbiol. Immunol. 105:1.PubMedCrossRefGoogle Scholar
  70. Thomas, S., Lamb, R. A., and Patterson, R. G., 1988, Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5, Cell 54:891.PubMedCrossRefGoogle Scholar
  71. Tinoco, I, Borer, P. N., Dengler, B., Levine, M. D., Uhlenbeck, O. C., Crothers, D. M., and Gralla, J., 1973, Improved estimation of secondary structure in ribonucleic acids, Nat. New Biol. 246:40.PubMedGoogle Scholar
  72. Valsamakis, A., Riviere, Y., and Oldstone, M. B. A., 1987, Perturbation of differentiated functions in vivo during persistent viral infection, Virology 156:214.PubMedCrossRefGoogle Scholar
  73. van der Werf, S., Bradley, J., Wimmer, E., Studier, W., and Dunn, J. J., 1986, Synthesis of infectious poliovirus RNA by purified T7 RNA polymerase, Proc. Natl. Acad. Sci. USA 83:2330.PubMedCrossRefGoogle Scholar
  74. Vezza, A. C., Gard, G. P., Compans, R. W., and Bishop, D. H. L., 1977, Structural components of the arenavirus Pichinde, J. Virol. 23:776.PubMedGoogle Scholar
  75. Vezza, A C, Clewley, J. P., Gard, G. P., Abraham, N Z, Compans, R. W., and Bishop, D. H. L., 1978a, Virion RNA species of the Arenaviruses Pichinde, Tacaribe, and Tamiami, J. Virol. 26:485.Google Scholar
  76. Vezza, A. C., Gard, G. P., Compans, R. W., and Bishop, D. H. L., 1978b, Genetic and molecular studies of arenaviruses, in: Negative Strand Viruses and the Host Cell (B. W. J. Mahy and R. D. Barry, eds.), pp. 73. Academic Press. New York.Google Scholar
  77. Whitton, J. L., Southern, P. J., and Oldstone, M. B. A., 1988, Analysis of the cytotoxic T-lymphocyte response to glycoprotein and nucleoprotein components of lymphocytic choriomeningitis virus, Virology 16:321.CrossRefGoogle Scholar
  78. Whitton, J. L., Tishon, A., Lewicki, H., Gebhard, J., Cook, T., Salvato, M. S., Joly, E., and Oldstone, M. B. A., 1989, Molecular analyses of a five-amino-acid cytotoxic T lymphocyte (CTL) epitope: An immunodominant region which induces nonreciprocal CTL cross-reactivity, J. Virol. 63:4303.PubMedGoogle Scholar
  79. Wu, H-N., and Lai, M. M. C., 1989, Reversible cleavage and ligation of hepatitis delta virus RNA, Science 243:652.PubMedCrossRefGoogle Scholar
  80. Zinkernagel, R. M., and Doherty, P. C., 1974, Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis virus with a syngeneic or semiallogeneic system, Nature 248:701.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Maria S. Salvato
    • 1
  1. 1.Department of Pathology and Laboratory MedicineUniversity of WisconsinMadisonUSA

Personalised recommendations