Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 May 1;167(5):1719–1724. doi: 10.1084/jem.167.5.1719

Organ-specific selection of viral variants during chronic infection [published erratum appears in J Exp Med 1988 Jul 1;168(1):457]

PMCID: PMC2188938  PMID: 3367096

Abstract

This study demonstrates organ specific selection of viral variants during chronic lymphocytic choriomeningitis virus (LCMV) infection in its natural host. Isolates with different biological properties were present in the central nervous system (CNS) and lymphoid tissues of carrier mice infected at birth with the wt Armstrong strain of LCMV. Viral isolates from the CNS were similar to the wt Armstrong strain and induced potent virus-specific cytotoxic T lymphocyte (CTL) responses in adult mice and the infection was cleared within 2 wk. In contrast, LCMV isolates derived from the lymphoid tissues caused a chronic infection in adult mice associated with suppressed CTL responses. Revertants with wt Armstrong phenotype were present in the CNS of mice infected with a spleen isolate showing unequivocally the importance of host tissues in the selection of viral variants. These results provide a possible mechanism by which viral variants emerge in nature and suggest that tissue- and cell-specific selection is an important aspect of virus evolution.

Full Text

The Full Text of this article is available as a PDF (366.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahmed R., Canning W. M., Kauffman R. S., Sharpe A. H., Hallum J. V., Fields B. N. Role of the host cell in persistent viral infection: coevolution of L cells and reovoirus during persistent infection. Cell. 1981 Aug;25(2):325–332. doi: 10.1016/0092-8674(81)90050-7. [DOI] [PubMed] [Google Scholar]
  2. Ahmed R., King C. C., Oldstone M. B. Virus-lymphocyte interaction: T cells of the helper subset are infected with lymphocytic choriomeningitis virus during persistent infection in vivo. J Virol. 1987 May;61(5):1571–1576. doi: 10.1128/jvi.61.5.1571-1576.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ahmed R., Salmi A., Butler L. D., Chiller J. M., Oldstone M. B. Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence. J Exp Med. 1984 Aug 1;160(2):521–540. doi: 10.1084/jem.160.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benn S., Rutledge R., Folks T., Gold J., Baker L., McCormick J., Feorino P., Piot P., Quinn T., Martin M. Genomic heterogeneity of AIDS retroviral isolates from North America and Zaire. Science. 1985 Nov 22;230(4728):949–951. doi: 10.1126/science.2997922. [DOI] [PubMed] [Google Scholar]
  5. Buchmeier M. J., Lewicki H. A., Tomori O., Oldstone M. B. Monoclonal antibodies to lymphocytic choriomeningitis and pichinde viruses: generation, characterization, and cross-reactivity with other arenaviruses. Virology. 1981 Aug;113(1):73–85. doi: 10.1016/0042-6822(81)90137-9. [DOI] [PubMed] [Google Scholar]
  6. Gilden D. H., Cole G. A., Monjan A. A., Nathanson N. Immunopathogenesis of acute central nervous system disease produced by lymphocytic choriomeningitis virus. I. Cyclophosphamide-mediated induction by the virus-carrier state in adult mice. J Exp Med. 1972 Apr 1;135(4):860–873. doi: 10.1084/jem.135.4.860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hahn B. H., Shaw G. M., Taylor M. E., Redfield R. R., Markham P. D., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Parks E. S., Parks W. P. Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science. 1986 Jun 20;232(4757):1548–1553. doi: 10.1126/science.3012778. [DOI] [PubMed] [Google Scholar]
  8. Holland J., Spindler K., Horodyski F., Grabau E., Nichol S., VandePol S. Rapid evolution of RNA genomes. Science. 1982 Mar 26;215(4540):1577–1585. doi: 10.1126/science.7041255. [DOI] [PubMed] [Google Scholar]
  9. Hotchin J., Kinch W., Benson L. Lytic and turbid plaque-type mutants of lymphocytic choriomeningitis virus as a cause of neurological disease or persistent infection. Infect Immun. 1971 Sep;4(3):281–286. doi: 10.1128/iai.4.3.281-286.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kono Y., Kobayashi K., Fukunaga Y. Antigenic drift of equine infectious anemia virus in chronically infected horses. Arch Gesamte Virusforsch. 1973;41(1):1–10. doi: 10.1007/BF01249923. [DOI] [PubMed] [Google Scholar]
  11. Koyanagi Y., Miles S., Mitsuyasu R. T., Merrill J. E., Vinters H. V., Chen I. S. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science. 1987 May 15;236(4803):819–822. doi: 10.1126/science.3646751. [DOI] [PubMed] [Google Scholar]
  12. Narayan O., Griffin D. E., Chase J. Antigenic shift of visna virus in persistently infected sheep. Science. 1977 Jul 22;197(4301):376–378. doi: 10.1126/science.195339. [DOI] [PubMed] [Google Scholar]
  13. Pfau C. J., Valenti J. K., Jacobson S., Pevear D. C. Cytotoxic T cells are induced in mice infected with lymphocytic choriomeningitis virus strains of markedly different pathogenicities. Infect Immun. 1982 May;36(2):598–602. doi: 10.1128/iai.36.2.598-602.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Popescu M., Lehmann-Grube F. Diversity of lymphocytic choriomeningitis virus: variation due to replication of the virus in the mouse. J Gen Virol. 1976 Jan;30(1):113–122. doi: 10.1099/0022-1317-30-1-113. [DOI] [PubMed] [Google Scholar]
  15. Rodriguez M., Buchmeier M. J., Oldstone M. B., Lampert P. W. Ultrastructural localization of viral antigens in the CNS of mice persistently infected with lymphocytic choriomeningitis virus (LCMV). Am J Pathol. 1983 Jan;110(1):95–100. [PMC free article] [PubMed] [Google Scholar]
  16. Southern P. J., Singh M. K., Riviere Y., Jacoby D. R., Buchmeier M. J., Oldstone M. B. Molecular characterization of the genomic S RNA segment from lymphocytic choriomeningitis virus. Virology. 1987 Mar;157(1):145–155. doi: 10.1016/0042-6822(87)90323-0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES