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. 1996;107:89–98.

The Gordon Wilson lecture: unique interactions between viruses, neurons and the immune system.

D E Griffin 1
PMCID: PMC2376553  PMID: 8725563

Abstract

The increased susceptibility of young individuals to alphavirus encephalitis is likely to be linked to the ease with which immature neurons are induced to undergo apoptosis after infection. In the more mature individuals, virus infection of neurons may not lead to apoptosis and in the absence of an effective immune response persistent infection is established. The major mechanism by which alphavirus infection of neurons is controlled is by production and local secretion of antibody to the surface glycoproteins. Antibody acts synergistically with interferon to decrease intracellular virus replication but does not eliminate the infected cell or the viral RNA within the cell. Therefore, the immune response controls, but does not cure the infection, leading to a requirement for long-term local synthesis of antiviral antibody in the CNS. For the host persistent intracellular RNA and need for longterm control is probably a reasonable price to pay for a noncytolytic mechanism for control of neuronal viral infection.

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Selected References

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

  1. Bashford C. L., Alder G. M., Gray M. A., Micklem K. J., Taylor C. C., Turek P. J., Pasternak C. A. Oxonol dyes as monitors of membrane potential: the effect of viruses and toxins on the plasma membrane potential of animal cells in monolayer culture and in suspension. J Cell Physiol. 1985 Jun;123(3):326–336. doi: 10.1002/jcp.1041230306. [DOI] [PubMed] [Google Scholar]
  2. Calisher C. H. Medically important arboviruses of the United States and Canada. Clin Microbiol Rev. 1994 Jan;7(1):89–116. doi: 10.1128/cmr.7.1.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Daar A. S., Fuggle S. V., Fabre J. W., Ting A., Morris P. J. The detailed distribution of HLA-A, B, C antigens in normal human organs. Transplantation. 1984 Sep;38(3):287–292. doi: 10.1097/00007890-198409000-00018. [DOI] [PubMed] [Google Scholar]
  4. David-Watine B., Israël A., Kourilsky P. The regulation and expression of MHC class I genes. Immunol Today. 1990 Aug;11(8):286–292. doi: 10.1016/0167-5699(90)90114-o. [DOI] [PubMed] [Google Scholar]
  5. Després P., Griffin J. W., Griffin D. E. Antiviral activity of alpha interferon in Sindbis virus-infected cells is restored by anti-E2 monoclonal antibody treatment. J Virol. 1995 Nov;69(11):7345–7348. doi: 10.1128/jvi.69.11.7345-7348.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Després P., Griffin J. W., Griffin D. E. Effects of anti-E2 monoclonal antibody on sindbis virus replication in AT3 cells expressing bcl-2. J Virol. 1995 Nov;69(11):7006–7014. doi: 10.1128/jvi.69.11.7006-7014.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Garry R. F. Sindbis virus-induced inhibition of protein synthesis is partially reversed by medium containing an elevated potassium concentration. J Gen Virol. 1994 Feb;75(Pt 2):411–415. doi: 10.1099/0022-1317-75-2-411. [DOI] [PubMed] [Google Scholar]
  8. Garry R. F., Waite M. R. Na+ and K+ concentrations and the regulation of the interferon system in chick cells. Virology. 1979 Jul 15;96(1):121–128. doi: 10.1016/0042-6822(79)90178-8. [DOI] [PubMed] [Google Scholar]
  9. Griffin D. E. Role of the immune response in age-dependent resistance of mice to encephalitis due to Sindbis virus. J Infect Dis. 1976 Apr;133(4):456–464. doi: 10.1093/infdis/133.4.456. [DOI] [PubMed] [Google Scholar]
  10. Hahn C. S., Lustig S., Strauss E. G., Strauss J. H. Western equine encephalitis virus is a recombinant virus. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5997–6001. doi: 10.1073/pnas.85.16.5997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jackson A. C., Moench T. R., Griffin D. E., Johnson R. T. The pathogenesis of spinal cord involvement in the encephalomyelitis of mice caused by neuroadapted Sindbis virus infection. Lab Invest. 1987 Apr;56(4):418–423. [PubMed] [Google Scholar]
  12. Jackson A. C., Moench T. R., Trapp B. D., Griffin D. E. Basis of neurovirulence in Sindbis virus encephalomyelitis of mice. Lab Invest. 1988 May;58(5):503–509. [PubMed] [Google Scholar]
  13. Johnson R. T., McFarland H. F., Levy S. E. Age-dependent resistance to viral encephalitis: studies of infections due to Sindbis virus in mice. J Infect Dis. 1972 Mar;125(3):257–262. doi: 10.1093/infdis/125.3.257. [DOI] [PubMed] [Google Scholar]
  14. Joly E., Mucke L., Oldstone M. B. Viral persistence in neurons explained by lack of major histocompatibility class I expression. Science. 1991 Sep 13;253(5025):1283–1285. doi: 10.1126/science.1891717. [DOI] [PubMed] [Google Scholar]
  15. Joly E., Oldstone M. B. Neuronal cells are deficient in loading peptides onto MHC class I molecules. Neuron. 1992 Jun;8(6):1185–1190. doi: 10.1016/0896-6273(92)90138-4. [DOI] [PubMed] [Google Scholar]
  16. Korsmeyer S. J. Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood. 1992 Aug 15;80(4):879–886. [PubMed] [Google Scholar]
  17. LONGSHORE W. A., Jr, STEVENS I. M., HOLLISTER A. C., Jr, GITTELSOHN A., LENNETTE E. H. Epidemiologic observations on acute infectious encephalitis in California, with special reference to the 1952 outbreak. Am J Hyg. 1956 Jan;63(1):69–86. doi: 10.1093/oxfordjournals.aje.a119793. [DOI] [PubMed] [Google Scholar]
  18. Levine B., Griffin D. E. Persistence of viral RNA in mouse brains after recovery from acute alphavirus encephalitis. J Virol. 1992 Nov;66(11):6429–6435. doi: 10.1128/jvi.66.11.6429-6435.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Levine B., Hardwick J. M., Trapp B. D., Crawford T. O., Bollinger R. C., Griffin D. E. Antibody-mediated clearance of alphavirus infection from neurons. Science. 1991 Nov 8;254(5033):856–860. doi: 10.1126/science.1658936. [DOI] [PubMed] [Google Scholar]
  20. Levine B., Huang Q., Isaacs J. T., Reed J. C., Griffin D. E., Hardwick J. M. Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature. 1993 Feb 25;361(6414):739–742. doi: 10.1038/361739a0. [DOI] [PubMed] [Google Scholar]
  21. McFarland H. F., Griffin D. E., Johnson R. T. Specificity of the inflammatory response in viral encephalitis. I. Adoptive immunization of immunosuppressed mice infected with Sindbis virus. J Exp Med. 1972 Aug 1;136(2):216–226. doi: 10.1084/jem.136.2.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Noran H. H. Chronic Equine Encephalitis. Am J Pathol. 1944 Mar;20(2):259–267. [PMC free article] [PubMed] [Google Scholar]
  23. Nuñez G., Clarke M. F. The Bcl-2 family of proteins: regulators of cell death and survival. Trends Cell Biol. 1994 Nov;4(11):399–403. doi: 10.1016/0962-8924(94)90053-1. [DOI] [PubMed] [Google Scholar]
  24. Sherman L. A., Griffin D. E. Pathogenesis of encephalitis induced in newborn mice by virulent and avirulent strains of Sindbis virus. J Virol. 1990 May;64(5):2041–2046. doi: 10.1128/jvi.64.5.2041-2046.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Strauss J. H., Strauss E. G. The alphaviruses: gene expression, replication, and evolution. Microbiol Rev. 1994 Sep;58(3):491–562. doi: 10.1128/mr.58.3.491-562.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tyor W. R., Wesselingh S., Levine B., Griffin D. E. Long term intraparenchymal Ig secretion after acute viral encephalitis in mice. J Immunol. 1992 Dec 15;149(12):4016–4020. [PubMed] [Google Scholar]
  27. Ubol S., Levine B., Lee S. H., Greenspan N. S., Griffin D. E. Roles of immunoglobulin valency and the heavy-chain constant domain in antibody-mediated downregulation of Sindbis virus replication in persistently infected neurons. J Virol. 1995 Mar;69(3):1990–1993. doi: 10.1128/jvi.69.3.1990-1993.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ulug E. T., Bose H. R., Jr Effect of tunicamycin on the development of the cytopathic effect in Sindbis virus-infected avian fibroblasts. Virology. 1985 Jun;143(2):546–557. doi: 10.1016/0042-6822(85)90393-9. [DOI] [PubMed] [Google Scholar]
  29. Ulug E. T., Garry R. F., Bose H. R., Jr The role of monovalent cation transport in Sindbis virus maturation and release. Virology. 1989 Sep;172(1):42–50. doi: 10.1016/0042-6822(89)90105-0. [DOI] [PubMed] [Google Scholar]
  30. Ulug E. T., Garry R. F., Waite M. R., Bose H. R., Jr Alterations in monovalent cation transport in Sindbis virus-infected chick cells. Virology. 1984 Jan 15;132(1):118–130. doi: 10.1016/0042-6822(84)90096-5. [DOI] [PubMed] [Google Scholar]
  31. VILCEK J. PRODUCTION OF INTERFERON BY NEWBORN AND ADULT MICE INFECTED WITH SINDBIS VIRUS. Virology. 1964 Apr;22:651–652. doi: 10.1016/0042-6822(64)90091-1. [DOI] [PubMed] [Google Scholar]
  32. Wesselingh S. L., Levine B., Fox R. J., Choi S., Griffin D. E. Intracerebral cytokine mRNA expression during fatal and nonfatal alphavirus encephalitis suggests a predominant type 2 T cell response. J Immunol. 1994 Feb 1;152(3):1289–1297. [PubMed] [Google Scholar]

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