1887

Abstract

Arenaviruses include several causative agents of haemorrhagic fever disease in humans. In addition, the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a superb model for the study of virus–host interactions, including the basis of viral persistence and associated diseases. There is little understanding about the molecular mechanisms concerning the regulation and specific role of viral proteins in modulating arenavirus–host cell interactions either associated with an acute or persistent infection, and associated disease. Here, we report the genomic and biological characterization of LCMV strains ‘Docile’ (persistent) and ‘Aggressive’ (not persistent) recovered from cloned cDNA via reverse genetics. Our results confirmed that the cloned viruses accurately recreated the phenotypes associated with the corresponding natural Docile and Aggressive viral isolates. In addition, we provide evidence that the ability of the Docile strain to persist is determined by the nature of both S and L RNA segments. Thus, our findings provide the foundation for studies aimed at gaining a detailed understanding of viral determinants of LCMV persistence in its natural host, which may aid in the development of vaccines to prevent or treat the diseases caused by arenaviruses in humans.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83464-0
2008-06-01
2024-12-07
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/6/1421.html?itemId=/content/journal/jgv/10.1099/vir.0.83464-0&mimeType=html&fmt=ahah

References

  1. Aebischer T., Moskophidis D., Rohrer U. H., Zinkernagel R. M., Hengartner H. 1991; In vitro selection of lymphocytic choriomeningitis virus escape mutants by cytotoxic T lymphocytes. Proc Natl Acad Sci U S A 88:11047–11051 [CrossRef]
    [Google Scholar]
  2. Ahmed R., Salmi A., Butler L. D., Chiller J. M., Oldstone M. B. 1984; 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 160:521–540 [CrossRef]
    [Google Scholar]
  3. Ahmed R., Morrrison L. A., Knipe D. M. 1996; Persistence of viruses. In Fields Virology pp 219–249Edited by Knipe D. M., Howley P. M. Philadelphia: Lippincott-Raven;
    [Google Scholar]
  4. Battegay M., Cooper S., Althage A., Banziger J., Hengartner H., Zinkernagel R. M. 1991; Quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24- or 96-well plates. J Virol Methods 33:191–198 [CrossRef]
    [Google Scholar]
  5. Bergthaler A., Merkler D., Horvath E., Bestmann L., Pinschewer D. D. 2007; Contributions of the lymphocytic choriomeningitis virus glycoprotein and polymerase to strain-specific differences in murine liver pathogenicity. J Gen Virol 88:592–603 [CrossRef]
    [Google Scholar]
  6. 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. 1998; Identification of α -dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus. Science 282:2079–2081 [CrossRef]
    [Google Scholar]
  7. Damonte E. B., Coto C. E. 2002; Treatment of arenavirus infections: from basic studies to the challenge of antiviral therapy. Adv Virus Res 58:125–155
    [Google Scholar]
  8. Emonet S., Lemasson J. J., Gonzalez J. P., de Lamballerie X., Charrel R. N. 2006; Phylogeny and evolution of old world arenaviruses. Virology 350:251–257 [CrossRef]
    [Google Scholar]
  9. Flatz L., Bergthaler A., de la Torre J. C., Pinschewer D. D. 2006; Recovery of an arenavirus entirely from RNA polymerase I/II-driven cDNA. Proc Natl Acad Sci U S A 103:4663–4668 [CrossRef]
    [Google Scholar]
  10. Garcin D., Kolakofsky D. 1990; A novel mechanism for the initiation of Tacaribe arenavirus genome replication. J Virol 64:6196–6203
    [Google Scholar]
  11. Hotchin J. 1971; Persistent and slow virus infections. In Monographs Virology pp 1–211 Vienna: Springer-Verlag;
    [Google Scholar]
  12. Jay M. T., Glaser C., Fulhorst C. F. 2005; The arenaviruses. J Am Vet Med Assoc 227:904–915 [CrossRef]
    [Google Scholar]
  13. Kotturi M. F., Peters B., Buendia-Laysa F., Sidney, , J., Oseroff C., Botten J., Grey H., Buchmeier M. J., Sette A. 2007; The CD8+ T-cell response to lymphocytic choriomeningitis virus involves the L antigen: uncovering new tricks for an old virus. J Virol 81:4928–4940 [CrossRef]
    [Google Scholar]
  14. Kunz S., Borrow P., Oldstone M. B. 2002; Receptor structure, binding, and cell entry of arenaviruses. Curr Top Microbiol Immunol 262:111–137
    [Google Scholar]
  15. Kunz S., Edelmann K. H., de la Torre J. C., Gorney R., Oldstone M. B. 2003; Mechanisms for lymphocytic choriomeningitis virus glycoprotein cleavage, transport, and incorporation into virions. Virology 314:168–178 [CrossRef]
    [Google Scholar]
  16. Lee K. J., Novella I. S., Teng M. N., Oldstone M. B., de La Torre J. C. 2000; NP and L proteins of lymphocytic choriomeningitis virus (LCMV) are sufficient for efficient transcription and replication of LCMV genomic RNA analogs. J Virol 74:3470–3477 [CrossRef]
    [Google Scholar]
  17. Lehmann-Grube F. 1972; Persistent infection of the mouse with the virus of lymphocytic choriomeningitis. J Clin Pathol Suppl (R Coll Pathol) 6:8–21
    [Google Scholar]
  18. Leist T. P., Ruedi E., Zinkernagel R. M. 1988; Virus-triggered immune suppression in mice caused by virus-specific cytotoxic T cells. J Exp Med 167:1749–1754 [CrossRef]
    [Google Scholar]
  19. Lewicki H. A., Von Herrath M. G., Evans C. F., Whitton J. L., Oldstone M. B. 1995; CTL escape viral variants. II. Biologic activity in vivo. Virology 211:443–450 [CrossRef]
    [Google Scholar]
  20. Lukashevich I. S. 1992; Generation of reassortants between African arenaviruses. Virology 188:600–605 [CrossRef]
    [Google Scholar]
  21. Lukashevich I. S., Patterson J., Carrion R., Moshkoff D., Ticer A., Zapata J., Brasky K., Geiger R., Hubbard G. B. other authors 2005; A live attenuated vaccine for Lassa fever made by reassortment of Lassa and Mopeia viruses. J Virol 79:13934–13942 [CrossRef]
    [Google Scholar]
  22. Martinez-Sobrido L., Zuniga E. I., Rosario D., Garcia-Sastre A., de la Torre J. C. 2006; Inhibition of the type I interferon response by the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus. J Virol 80:9192–9199 [CrossRef]
    [Google Scholar]
  23. Matloubian M., Kolhekar S. R., Somasundaram T., Ahmed R. 1993; Molecular determinants of macrophage tropism and viral persistence: importance of single amino acid changes in the polymerase and glycoprotein of lymphocytic choriomeningitis virus. J Virol 67:7340–7349
    [Google Scholar]
  24. Meyer B. J., Southern P. J. 1993; Concurrent sequence analysis of 5′ and 3′ RNA termini by intramolecular circularization reveals 5′ nontemplated bases and 3′ terminal heterogeneity for lymphocytic choriomeningitis virus mRNAs. J Virol 67:2621–2627
    [Google Scholar]
  25. Meyer B. J., Southern P. J. 1997; A novel type of defective viral genome suggests a unique strategy to establish and maintain persistent lymphocytic choriomeningitis virus infections. J Virol 71:6757–6764
    [Google Scholar]
  26. Meyer B. J., de la Torre J. C., Southern P. J. 2002; Arenaviruses: genomic RNAs, transcription, and replication. Curr Top Microbiol Immunol 262:139–157
    [Google Scholar]
  27. Moskophidis D., Lehmann-Grube F. 1989; Virus-induced delayed-type hypersensitivity reaction is sequentially mediated by CD8+ and CD4+ T lymphocytes. Proc Natl Acad Sci U S A 86:3291–3295 [CrossRef]
    [Google Scholar]
  28. Moskophidis D., Zinkernagel R. M. 1995; Immunobiology of cytotoxic T-cell escape mutants of lymphocytic choriomeningitis virus. J Virol 69:2187–2193
    [Google Scholar]
  29. Moskophidis D., Lechner F., Pircher H., Zinkernagel R. M. 1993; Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells. Nature 362:758–761 [CrossRef]
    [Google Scholar]
  30. Moskophidis D., Battegay M., Bruendler M. A., Laine E., Gresser I., Zinkernagel R. M. 1994; Resistance of lymphocytic choriomeningitis virus to alpha/beta interferon and to gamma interferon. J Virol 68:1951–1955
    [Google Scholar]
  31. Moskophidis D., Battegay M., van den Broek M., Laine E., Hoffmann-Rohrer U., Zinkernagel R. M. 1995; Role of virus and host variables in virus persistence or immunopathological disease caused by a non-cytolytic virus. J Gen Virol 76:381–391 [CrossRef]
    [Google Scholar]
  32. Mueller S. N., Matloubian M., Clemens D. M., Sharpe A. H., Freeman G. J., Gangappa S., Larsen C. P., Ahmed R. 2007; Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection. Proc Natl Acad Sci U S A 104:15430–15435 [CrossRef]
    [Google Scholar]
  33. Oldstone M. B. 2006; Viral persistence: parameters, mechanisms and future predictions. Virology 344:111–118 [CrossRef]
    [Google Scholar]
  34. Oldstone M. B., Ahmed R., Salvato M. 1990; Viruses as therapeutic agents. II. Viral reassortants map prevention of insulin-dependent diabetes mellitus to the small RNA of lymphocytic choriomeningitis virus. J Exp Med 171:2091–2100 [CrossRef]
    [Google Scholar]
  35. Ou R., Zhou S., Huang L., Moskophidis D. 2001; Critical role for alpha/beta and gamma interferons in persistence of lymphocytic choriomeningitis virus by clonal exhaustion of cytotoxic T cells. J Virol 75:8407–8423 [CrossRef]
    [Google Scholar]
  36. Pannetier C., Cochet M., Darche S., Kourilsky P. 1992; Quantitative determination method of nucleic acids by enzymatic amplification (PCR method) to saturation. C R Acad Sci III 315:271–277 (in French
    [Google Scholar]
  37. Perez M., Craven R. C., de la Torre J. C. 2003; The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies. Proc Natl Acad Sci U S A 100:12978–12983 [CrossRef]
    [Google Scholar]
  38. Peters C. J. 2002; Human infection with arenaviruses in the Americas. Curr Top Microbiol Immunol 262:65–74
    [Google Scholar]
  39. Pfau C. J., Valenti J. K., Pevear D. C., Hunt K. D. 1982; Lymphocytic choriomeningitis virus killer T cells are lethal only in weakly disseminated murine infections. J Exp Med 156:79–89 [CrossRef]
    [Google Scholar]
  40. Pinschewer D. D., Perez M., de la Torre J. C. 2005; Dual role of the lymphocytic choriomeningitis virus intergenic region in transcription termination and virus propagation. J Virol 79:4519–4526 [CrossRef]
    [Google Scholar]
  41. Pircher H., Moskophidis D., Rohrer U., Burki K., Hengartner H., Zinkernagel R. M. 1990; Viral escape by selection of cytotoxic T cell-resistant virus variants in vivo. Nature 346:629–633 [CrossRef]
    [Google Scholar]
  42. Radoshitzky S. R., Abraham J., Spiropoulou C. F., Kuhn J. H., Nguyen D., Li W., Nagel J., Schmidt P. J., Nunberg J. H. other authors 2007; Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature 446:92–96 [CrossRef]
    [Google Scholar]
  43. Riviere Y., Ahmed R., Southern P. J., Buchmeier M. J., Oldstone M. B. 1985; Genetic mapping of lymphocytic choriomeningitis virus pathogenicity: virulence in guinea pigs is associated with the L RNA segment. J Virol 55:704–709
    [Google Scholar]
  44. Romanowski V., Bishop D. H. 1985; Conserved sequences and coding of two strains of lymphocytic choriomeningitis virus (WE and ARM) and Pichinde arenavirus. Virus Res 2:35–51 [CrossRef]
    [Google Scholar]
  45. Salvato M., Borrow P., Shimomaye E., Oldstone M. B. 1991; Molecular basis of viral persistence: a 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 65:1863–1869
    [Google Scholar]
  46. Sanchez A. B., de la Torre J. C. 2006; Rescue of the prototypic Arenavirus LCMV entirely from plasmid. Virology 350:370–380 [CrossRef]
    [Google Scholar]
  47. Sevilla N., de la Torre J. C. 2006; Arenavirus diversity and evolution: quasispecies in vivo. Curr Top Microbiol Immunol 299:315–335
    [Google Scholar]
  48. Sevilla N., McGavern D. B., Teng C., Kunz S., Oldstone M. B. 2004; Viral targeting of hematopoietic progenitors and inhibition of DC maturation as a dual strategy for immune subversion. J Clin Invest 113:737–745 [CrossRef]
    [Google Scholar]
  49. Thomsen A. R., Johansen J., Marker O., Christensen J. P. 1996; Exhaustion of CTL memory and recrudescence of viremia in lymphocytic choriomeningitis virus-infected MHC class II-deficient mice and B cell-deficient mice. J Immunol 157:3074–3080
    [Google Scholar]
  50. Traub E. 1936; Persistence of lymphocytic choriomeningitis virus in immune animals and its relation to immunity. J Exp Med 63:847–861 [CrossRef]
    [Google Scholar]
  51. Zajac A. J., Blattman J. N., Murali-Krishna K., Sourdive D. J., Suresh M., Altman J. D., Ahmed R. 1998; Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med 188:2205–2213 [CrossRef]
    [Google Scholar]
  52. Zhang L., Marriott K. A., Harnish D. G., Aronson J. F. 2001; Reassortant analysis of guinea pig virulence of pichinde virus variants. Virology 290:30–38 [CrossRef]
    [Google Scholar]
  53. Zhou S., Ou R., Huang L., Price G. E., Moskophidis D. 2004; Differential tissue-specific regulation of antiviral CD8+ T-cell immune responses during chronic viral infection. J Virol 78:3578–3600 [CrossRef]
    [Google Scholar]
  54. Zinkernagel R. M., Moskophidis D., Kundig T., Oehen S., Pircher H., Hengartner H. 1993; Effector T-cell induction and T-cell memory versus peripheral deletion of T cells. Immunol Rev 133:199–223 [CrossRef]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.83464-0
Loading
/content/journal/jgv/10.1099/vir.0.83464-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error