Skip to main content
SpringerLink
Log in

Semliki Forest virus infection of laboratory mice: a model to study the pathogenesis of viral encephalitis

  • Chapter
Emergence and Control of Zoonotic Viral Encephalitides

Part of the book series: Archives of Virology. Supplementa ((ARCHIVES SUPPL,volume 18))

Summary

Semliki Forest virus (SFV) infection of the laboratory mouse provides an experimental system to study the pathogenesis of viral encephalitis. Following extra neural inoculation the virus is efficiently neuroinvasive and crosses the blood-brain barrier to initiate perivascular foci of infection in neurons and oligodendrocytes. The outcome of infection ranges from clinically unapparent mild encephalitis to fatal panencephalitis. SFV infections of the developing nervous system are always highly destructive and are generally fatal. In contrast, SFV infections of the mature nervous system can result in persistent infection with no apparent cell loss. This dramatic difference is attributable to developmental changes in the interactions between virus and CNS cells. Antibody responses clear the systemic infection and control the CNS infection. CD8+ T-cells are required to generate the lesions of inflammatory demyelination which can be a feature of the neuropathology. This article reviews the pathogenesis of SFV encephalitis, describing the neuropathology and the mechanisms which underlie it and which may be fundamental to many viral encephalitides.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Allsopp TE, Scallan MF, Williams A, Fazakerley JK (1998) Virus infection induces neuronal apoptosis: A comparison with trophic factor withdrawal. Cell Death Differ 5:50–59

    Article  PubMed  CAS  Google Scholar 

  2. Allsopp TE, Fazakerley JK (2000) Altruistic cell suicide and the specialized case of the virus-infected nervous system. Trends Neurosci 23:284–290

    Article  PubMed  CAS  Google Scholar 

  3. Amor S, Webb HE (1986) Use of normal-acetylethyleneimine [AEI] for the inactivation of Semliki Forest virus in vitro. J Med Virol 19:367–376

    Article  PubMed  CAS  Google Scholar 

  4. Amor S, Webb HE (1987) The effect of cycloleucine on SFV A7(74) infection in mice. Br J Exp Pathol 68:225–235

    PubMed  CAS  Google Scholar 

  5. Amor S, Webb HE (1988) CNS pathogenesis following a dual viral infection with Semliki Forest (alphavirus) and Langat (flavivirus). Br J Exp Pathol 69:197–208

    PubMed  CAS  Google Scholar 

  6. Amor S, Scallan MF, Morris MM, Dyson H, Fazakerley JK (1996) Role of immune responses in protection and pathogenesis during Semliki Forest virus encephalitis. J Gen Virol 77:281–291

    Article  PubMed  CAS  Google Scholar 

  7. Atkins GJ, Sheahan BJ, Liljestrom P (1999) The molecular pathogenesis of Semliki Forest virus: a model virus made useful. J Gen Virol 80:2287–2297

    PubMed  CAS  Google Scholar 

  8. Balluz IM, Glasgow GM, Killen HM, Mabruk MJ, Sheahan BJ, Atkins GJ (1993) Virulent and avirulent strains of Semliki Forest virus show similar cell tropism for the murine central nervous system but differ in the severity and rate of induction of cytolytic damage. Neuropathol Appl Neurobiol 19:233–239

    Article  PubMed  CAS  Google Scholar 

  9. Benbough JE (1969) The effect of relative humidity on the survival of airborne Semliki Forest virus. J Gen Virol 4:473–477

    Article  PubMed  CAS  Google Scholar 

  10. Berglund P, Tubulekas I, Liljestrom P (1996) Alphaviruses as vectors for gene delivery. Trends Biotechnol 14:130–134

    Article  PubMed  CAS  Google Scholar 

  11. Boere WA, Benaissa-Trouw BJ, Harmsen M, Kraaijeveld CA, Snippe H (1983) Neutralizing and non-neutralizing monoclonal antibodies to the E2 glycoprotein of Semliki Forest virus can protect mice from lethal encephalitis. J Gen Virol 64:1405–1408

    Article  PubMed  CAS  Google Scholar 

  12. Boere WA, Harmsen T, Vinje J, Benaissa-Trouw BJ, Kraaijeveld CA, Snippe H (1984) Identification of distinct antigenic determinants on Semliki Forest virus by using monoclonal antibodies with different antiviral activities. J Virol 52:575–582

    PubMed  CAS  Google Scholar 

  13. Bradish CJ, Allner K, Maber HB (1971) The virulence of original and derived strains of Semliki Forest virus for mice, guinea-pigs and rabbits. J Gen Virol 12:141–160

    Article  PubMed  CAS  Google Scholar 

  14. Bradish CJ, Allner K, Fitzgeorge R (1975) Immunomodification and the expression of virulence in mice by defined strains of Semliki Forest virus: the effects of cyclophosphamide. J Gen Virol 28:225–237

    Article  PubMed  CAS  Google Scholar 

  15. de Jong JC, Harmsen M, Plantinga AD, Trouwbrost T (1976) Inactivation of Semliki Forest virus in aerosols. Appl Environ Microbiol 32:315–319

    PubMed  Google Scholar 

  16. Donnelly SM, Sheahan BJ, Atkins GJ (1997) Long-term effects of Semliki Forest virus infection in the mouse central nervous system. Neuropathol Appl Neurobiol 23:235–241

    Article  PubMed  CAS  Google Scholar 

  17. Fazakerley JK, Webb HE (1987a) Semliki Forest virus-induced, immune-mediated demyelination: adoptive transfer studies and viral persistence in nude mice. J Gen Virol 68:377–385

    Article  PubMed  CAS  Google Scholar 

  18. Fazakerley JK, Webb HE (1987b) Cyclosporine enhances viraIly induced T-cell-mediated demyelination. The effect of cyclosporine on a demyelinating virus infection. J Neurol Sci 78:35–50

    Article  PubMed  CAS  Google Scholar 

  19. Fazakerley JK, Webb HE (1987c) Semliki Forest virus induced, immune mediated demyelination: the effect of irradiation. Br J Exp Pathol 68:101–113

    PubMed  CAS  Google Scholar 

  20. Fazakerley JK, Pathak S, Scallan M, Amor S, Dyson H (1993) Replication of the A7(74) strain of Semliki Forest virus is restricted in neurons. Virology 195:627–637

    Article  PubMed  CAS  Google Scholar 

  21. Fazakerley JK, Buchmeier MJ (1993) Pathogenesis of virus-induced demyelination. Adv Virus Res 42:249–324

    Article  PubMed  CAS  Google Scholar 

  22. Fazakerley JK, Amor S, Nash AA (1997) Animal model systems of MS. In: Russell WC (ed), Molecular biology of multiple sclerosis. John Wiley & Sons, Clinchster, pp 255–273

    Google Scholar 

  23. Fazakerley JK (2001) Neurovirology and developmental neurobiology. Adv Virus Res 56:73–124

    Article  PubMed  CAS  Google Scholar 

  24. Fleeton MN, Chen M, Berglund P, Rhodes G, Parker SE, Murphy M, Atkins GJ, Liljestrom P (2001) Self-replicative RNA vaccines elicit protection against influenza A virus, respiratory syncytial virus, and a tickbome encephalitis virus. J Infect Dis 183:1395–1398

    Article  PubMed  CAS  Google Scholar 

  25. Fleming P (1977) Age-dependent and strain-related differences of virulence of Semliki Forest virus in mice. J Gen Viro 137:93–105

    Article  Google Scholar 

  26. Friedman RM, Levin JG, Grimley PM, Berezesky IK (1972) Membrane-associated replication complex in arbovirus infection. J Virol 10:504–515

    PubMed  CAS  Google Scholar 

  27. Garoff H, Frischauf A, Simons K, Lehrach H, Delius H (1980) Nucleotide sequence of cDNA coding for Semliki Forest virus membrane glycoproteins. Nature 288:236–241

    Article  PubMed  CAS  Google Scholar 

  28. Glasgow GM, Killen HM, Liljestrom P, Sheahan BJ, Atkins GJ (1994) A single amino acid change in the E2 spike protein of a virulent strain of Semliki Forest virus attenuates pathogenicity. J Gen Virol 75:663–668

    Article  PubMed  CAS  Google Scholar 

  29. Grimley PM, Berezesky IK, Friedman RM (1968) Cytoplasmic structures associated with an arbovirus infection: loci of viral ribonucleic acid synthesis. J Virol 2:1326–1338

    PubMed  CAS  Google Scholar 

  30. Grimley PM, Friedman RM (1970) Development of Semliki Forest virus in mouse brain — An electron microscopic study. Exp Mol Pathol 12:1–13

    Article  PubMed  CAS  Google Scholar 

  31. Helenius A, Morein B, Fries E, Simons K, Robinson P, Schirmaer V (1978) Human (HLA-A and HLA-B) and murine (H-2k) and (H-2d) histocompatibility antigens are cell surface receptors for Semliki Forest virus. Proc Natl Acad Sci USA 75:3846–3850

    Article  PubMed  CAS  Google Scholar 

  32. Jagelman S, Suckling AJ, Webb HE, Bowen ETW (1978) The pathogenesis of avirulent Semliki Forest virus infections in athymic nude mice. J Gen Virol 41:599–607

    Article  PubMed  CAS  Google Scholar 

  33. Kaluza G, Lell G, Reinacher M, Stitz L, Willems WR (1987) Neurogenic spread of Semliki Forest virus in mice. Arch Virol 93:97–110

    Article  PubMed  CAS  Google Scholar 

  34. Kelly WR, Blakemore WF, Jagelman S, Webb HE (1982) Demyelination induced in mice by avirulent Semliki Forest virus. II. An ultrastructural study of focal demyelination in the brain. Neuropathol Appl Neurobiol 8:43–53

    Article  PubMed  CAS  Google Scholar 

  35. Kielian M, Helenius A (1984) pH-induced changes in the fusogenic spike protein of Semliki Forest virus. J Cell Biol 101:2284–2291

    Google Scholar 

  36. Kraaijeveld CA, Harmsen M, Khader Boutahar-Trouw B (1979) Delayed-type hypersensitivity against Semliki Forest virus. Infect Immun 23:217–221

    Google Scholar 

  37. Kujala P, Ikaheimonen A, Ehsani N, Vihinen H, Auvinen P, Kaariainen L (2001) Biogenesis of the Semliki Forest virus RNA replication complex. J Virol 75:3873–3884

    Article  PubMed  CAS  Google Scholar 

  38. Liljestrom P, Garoff H (1991) A new generation of animal cell expression vectors based on the Semliki Forest virus replicon. Biotechnology 9:1356–1361

    Article  PubMed  CAS  Google Scholar 

  39. Marsh M, Kielian MC, Helenius A (1984) Semliki Forest virus entry and the endocytic pathway. Biochem Soc Trans 12:981–983

    PubMed  CAS  Google Scholar 

  40. Mathiot CC, Grimaud G, Garry P, Bouquety JC, Mada A, Daguisy AM, Georges AJ (1990) An outbreak of human Semliki Forest virus infections in Central African Republic. Am J Trop Med Hyg 42:386–393

    PubMed  CAS  Google Scholar 

  41. Mehta S, Pathak S, Webb HE (1990) Induction of membrane proliferation in mouse CNS by gold sodium thiomalate with reference to increased virulence of the avirulent Semliki Forest virus. Biosci Rep 10:271–279

    Article  PubMed  CAS  Google Scholar 

  42. Mokhtarian F, Swoveland P (1987) Predisposition to EAE induction in resistant mice by prior infection with Semliki Forest virus. J Immunol 138:3264–3268

    PubMed  CAS  Google Scholar 

  43. Mokhtarian F, Shi Y, Grob D (1996) Epitopes ofSemliki Forest virus which evoke crossreactive immune-response with peptides of the central-nervous-system. FASEB J 10:2092–2092

    Google Scholar 

  44. Morris MM, Dyson H, Baker D, Harbige LS, Fazakerley JK, Amor S (1997) Characterization of the cellular and cytokine response in the central nervous system following Semliki Forest virus infection. J Neuroimmunol 74:185–197

    Article  PubMed  CAS  Google Scholar 

  45. Morris-Downes MM, Phenix KV, Smyth J, Sheahan BJ, Lileqvist S, Mooney DA, Liljestrom P, Todd D, Atkins GJ (2001) Semliki Forest virus-based vaccines: persistence, distribution and pathological analysis in two animal systems. Vaccine 19:1978–1988

    Article  PubMed  CAS  Google Scholar 

  46. Muller U, Steinhoff U, Reis L, Hemmi S, Pavlovic J, Zinkernagel RM, Aguet M (1994) Functional role of type I and type II interferons in antiviral defense. Science 264:1918–1921

    Article  PubMed  CAS  Google Scholar 

  47. Oliver KR, Scallan MF, Dyson H, Fazakerley JK (1997) Susceptibility to a neurotropic virus and its changing distribution in the developing brain is a function of CNS maturity. J Neurovirol 3:38–48

    Article  PubMed  CAS  Google Scholar 

  48. Oliver KR, Fazakerley JK (1998) Transneuronal spread of Semliki Forest virus in the developing mouse olfactory system is determined by neuronal maturity. Neurosci 82:867–877

    Article  CAS  Google Scholar 

  49. Omar A, Koblet H (1988) Semliki Forest virus-particles containing only the El envelope glycoprotein are infectious and can induce cell cell-fusion. Virology 166:17–23

    Article  PubMed  CAS  Google Scholar 

  50. Parsons LM, Webb HE (1982a) Blood brain barrier disturbance and immunoglobulin G levels in the cerebrospinal fluid of the mouse following peripheral infection with the demyelinating strain of Semliki Forest virus. J Neurol Sci 57:307–318

    Article  PubMed  CAS  Google Scholar 

  51. Parsons LM, Webb HE (1982b) Virus titers and persistently raised white cell counts in cerebrospinal-fluid in mice after peripheral infection with demyelinating Semliki Forest virus. Neuropathol Appl Neurobiol 8:395–401

    Article  PubMed  CAS  Google Scholar 

  52. Parsons LM, Webb HE (1984) Specific immunoglobulin G in serum and cerebrospinal fluid of mice infected with the demyelinating strain of Semliki Forest virus. Microbios Letters 25:135–140

    Google Scholar 

  53. Parsons LM, Webb HE (1989) Identification of immunoglobulin-containing cells in the central nervous system of the mouse following infection with the demyelinating strain of Semliki Forest virus. Br J Exp Pathol 70:247–255

    PubMed  CAS  Google Scholar 

  54. Pathak S, Webb HE (1974) Possible mechanisms for the transport of Semliki Forest virus into and within mouse brain: An electron microscopic study. J Neurol Sci 23:175–184

    Article  PubMed  CAS  Google Scholar 

  55. Pathak S, Webb HE, Oaten SW, Bateman S (1976) An electron-microscopic study of the development of virulent and avirulent strains of Semliki Forest virus in mouse brain. J Neurol Sci 28:289–300

    Article  PubMed  CAS  Google Scholar 

  56. Pathak S, Webb HE (1978) An electron-microscopic study of avirulent and virulent Semliki Forest virus in the brains of different ages of mice. J Neurol Sci 39:199–211

    Article  PubMed  CAS  Google Scholar 

  57. Pathak S, Webb HE (1983a) Semliki Forest virus multiplication in oligodendrocytes in mouse-brain with reference to demyelination. J Physiol (London) 339:17

    Google Scholar 

  58. Pathak S, Webb HE (1988a) Cytoplasmic viral core aggregates and budding of mature virus and spherules in mouse brain following Semliki Forest virus infections. Inst Phys Conf Ser 3:213–214

    Google Scholar 

  59. Pusztai R, Gould E, Smith H (1971) Infection pattern in mice of an avirulent and virulent strain of Semliki Forest virus. Br J Exp Pathol 52:669–677

    PubMed  CAS  Google Scholar 

  60. Santagati MG, Maatta JA, Itaranta PV, Salmi AA, Hinkkanen AE (1995) The Semliki Forest virus E2 gene as a virulence determinant. J Gen Virol 75:47–52

    Article  Google Scholar 

  61. Santagati MG, Maatta JA, Roytta M, Salmi AA, Hinkkanen AE (1998) The significance of the 3′-non translated region and E2 amino acid mutations in the virulence of Semliki Forest virus in mice. Virology 243:66–77

    Article  PubMed  CAS  Google Scholar 

  62. Scallan MF, Allsopp TE, Fazakerley JK (1997) bcl-2 acts early to restrict Semliki Forest virus replication and delays virus-induced programmed cell death. J Virol 71:1583–1590

    PubMed  CAS  Google Scholar 

  63. Scallan MF, Fazakerley JK (1999) Aurothiolates enhance the replication of Semliki Forest virus in the CNS and the exocrine pancreas. J Neurovirol 5:392–400

    Article  PubMed  CAS  Google Scholar 

  64. Smith JP, Morris-Downes M, Brennan FR, Wallace GJ, Amor S (2000) A role for alpha4-integrin in the pathology following Semliki Forest virus infection. J Neuroimmunol 106:60–68

    Article  PubMed  CAS  Google Scholar 

  65. Snijders A, Benaissa-Trouw BJ, Oosterlaken TA, Puijk WC, Posthumus WP, Meloen RH, Boere WA, Oosting JD, Kraaijeveld CA, Snippe H (1991) Identification of linear epitopes on Semliki Forest virus E2 membrane protein and their effectiveness as a synthetic peptide vaccine. J Gen Virol 72:557–565

    Article  PubMed  CAS  Google Scholar 

  66. Snijders A, Benaissatrouw BJ, Snippe H, Kraaijeveld CA (1992a) Immunogenicity and vaccine efficacy of synthetic peptides containing Semliki Forest virus B-cell and T-cell epitopes. J Gen Virol 73:2267–2272

    Article  PubMed  CAS  Google Scholar 

  67. Snijders A, Benaissatrouw BJ, Visservernooy HJ, Fernandez I, Snippe H, Kraaijeveld CA (1992b) A delayed-type hypersensitivity-inducing T-cell epitope of Semliki Forest virus mediates effective T-helper activity for antibody-production. Immunol 77:322–329

    CAS  Google Scholar 

  68. Soilu Hanninen M, Eralinna JP, Hukkanen V, Roytta M, Salmi AA, Salonen R (1994) Semliki-Forest virus infects mouse-brain endothelial-cells and causes blood-brain-barrier damage. J Virol 68:6291–6298

    PubMed  CAS  Google Scholar 

  69. Soilu Hanninen M, Roytta M, Salmi AA, Salonen R (1997) Semliki Forest virus infection leads to increased expression of adhesion molecules on splenic T-cells and on brain vascular endothelium. J Neurovirol 3:350–360

    Article  PubMed  CAS  Google Scholar 

  70. Subak-Sharpe I, Dyson H, Fazakerley JK (1993) In vivo depletion of CD8+ T cells prevents lesions of demyelination in Semliki Forest virus infection. J Viro1 67:7629–7633

    CAS  Google Scholar 

  71. Suckling AJ, Pathak S, Jagelman S, Webb HE (1978) Virus associated demyelination: a model using avirulent Semliki Forest virus infection of mice. J Neurol Sci 36:147–154

    Article  Google Scholar 

  72. Suckling AJ, Jagelman S, Webb HE (1982) Immunoglobulin synthesis in nude (nu/nu), nu/+ and reconstituted nu/nu mice infected with a demyelinating strain of Semliki Forest virus. Clin Exp Immunol 47:283–288

    PubMed  CAS  Google Scholar 

  73. Takkinen K (1986) Complete nucleotide-sequence of the non structural protein genes of Semliki Forest virus. Nucleic Acids Res 14:5667–5682

    Article  PubMed  CAS  Google Scholar 

  74. Wahlberga JM, Garoff H (1992) Membrane-fusion process of Semliki Forest virus. I. Low pH-induced rearrangement in spike protein quaternary structure precedes virus penetration into cells. J Cell Biol 116:339–348

    Article  Google Scholar 

  75. Willems WR, Kaluza G, Boschek GB, Bauer H (1979) Semliki Forest virus: Cause of a fatal case of human encephalitis. Science 203:1128–1129

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Infectious Diseases, College of Medicine and Veterinary Medicine, University of Edinburgh, Summerhall, Edinburgh, UK

    John K. Fazakerley

Authors
  1. John K. Fazakerley
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, USA

    Charles H. Calisher

  2. Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA

    Diane E. Griffin

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag Wien

About this chapter

Cite this chapter

Fazakerley, J.K. (2004). Semliki Forest virus infection of laboratory mice: a model to study the pathogenesis of viral encephalitis. In: Calisher, C.H., Griffin, D.E. (eds) Emergence and Control of Zoonotic Viral Encephalitides. Archives of Virology. Supplementa, vol 18. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0572-6_16

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-0572-6_16

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-20454-2

  • Online ISBN: 978-3-7091-0572-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation