Contribution of LCMV Towards Deciphering Biology of Quasispecies In Vivo

  • N. Sevilla
  • E. Domingo
  • J. C. de la Torre
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 263)


Arenaviruses have often been viewed as relatively stable genetically with amino acid sequence homologies of 90%–95% among different strains of lymphocytic choriomeningitis virus (LCMV) and of 44%–63% for homologous proteins of different arenaviruses: LCMV, Pichinde, Junin, Machupo and Lassa (Southern and Bishop 1987; Southern and Oldstone 1988). Yet considerable variation in biological properties among LCMV strains soon became apparent (reviewed in Dutko and Oldstone 1983; Southern and Oldstone 1988). Hotchin already recognized the importance of passage history in determining the biological properties of LCMV (Hotchin 1962). He showed that early mouse brain passages of LCMV-induced immunologic tolerance in newborn mice and mortality was low. In contrast, late mouse brain passages of LCMV lost the tolerance-inducing capacity, and mortality was high. Neonatal infection of certain mouse strains with LCMV strains Armstrong (ARM) and E-350-induced growth hormone deficiency and severe hypoglycemia, which frequently resulted in the death of the infected mice, while strains WE and Traub did not cause this syndrome. This difference was associated with the ability of LCMV ARM and E-350, but not WE and Traub, to replicate at high levels in the GH-producing cells in the anterior pituitary (Oldstone et al. 1985). Other biological differences among LCMV strains include the capacity of the virus to invade ß-cells in the islets of Langerhans, to cause alterations in glucose tolerance, or differences in the formation of immune complexes and lethality for adult guinea pigs (Southern and Oldstone 1988), as well as to induce generalized immunosuppression in adult mice. Selection of LCMV variants with distinguishable phenotypes occurs in different organs of infected mice persistently infected since birth with ARM tend to produce acute infection in adult mice, whereas isolates from the spleen of the same mice tend to persist (Ahmed and Oldstone 1988).


Human Immunodeficiency Virus Type Peripheral Blood Lymphocyte Viral Persistence Single Amino Acid Change Lassa Fever 
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Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • N. Sevilla
    • 1
  • E. Domingo
    • 2
  • J. C. de la Torre
    • 1
  1. 1.Department of NeuropharmacologyThe Scripps Research InstituteLa JollaUSA
  2. 2.Centro de Biologia Molecular Severo OchoaUniversidad Autonoma de MadridCantoblanco, MadridSpain

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