Skip to main content
NCBI home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 1992;16(1):45–58. doi: 10.1007/BF03159960

Potential role of viruses in neurodegeneration

Krister Kristensson 1,✉
PMCID: PMC7090832  PMID: 1520406

Abstract

Viruses have the capacity to induce alterations and degenerations of neurons by different direct and indirect mechanisms. In the review, we have focused on some examples that may provide new avenues for treatment or altering the course of infections, i.e., antibodies to fusogenic virus membrane proteins, drugs that interfere with lipid metabolism, calcium channel blockers, immunoregulatory molecules, and, and inhibitors of excitotoxic amino acids. Owing to their selectivity in attack on regions of nervous tissue, governed by viral factors and by routes of invasion, viral receptors or metabolic machineries of infected cells, certain viral infections show similarities in distribution of their resulting lesions in the nervous system to that of the common human neurodegenerative diseases (namely, motor neurons disease, Parkinson’s disease, and Alzheimer’s disease). However, it should be emphasized that no infectious agent has as yet provided a complete animal model for any of these diseases, nor has any infectious agent been linked to them from observations on clinical or postomortem materials.

Index Entries: Virus, nervous system, neurodegenerative diseases, ALS, Alzheimer’s disease, Parkinson’s disease, Creutzfeldt-Jakob’s disease, Gerstmann-Sträussler-Scheinker syndrome, motor neuron disease, virus, prion, protein synthesis, membranes, cytoskeleton, immunologic tolerance, glutamate, lipids, calcium, excitotoxic amino acids

References

  1. Allison J., Campbell I. L., Morahan G., Mandel T. E., Harrison C., Miller J. F. A. P. Diabetes in transgenic mice resulting from over-expression of class I histocompatibility molecules in pancreatic β cells. Nature. 1988;333:529–533. doi: 10.1038/333529a0. [DOI] [PubMed] [Google Scholar]
  2. Andersson T., Löve A., Schultzberg M., Norrby E., Kristensson K. Development of neuronal messengers in hamster retina with non-cytolytic mumps virus infection. Neurosci. Res. Comm. 1988;3:1–10. [Google Scholar]
  3. Andersson T., Wallén P., Grillner S., Norrby E., Kristensson K. A calcium-channel antagonist can prevent paramyxovirus-induced neurodegeneration. Neuroreport. 1991;2:145–148. doi: 10.1097/00001756-199103000-00009. [DOI] [PubMed] [Google Scholar]
  4. Andersson T., Schultzberg M., Schwarcz R., Löve A., Wickman C., Kristensson K. NMDA-receptor antagonist prevents measles virus-induced neurodegeneration. Eur. J. Neurosci. 1991;3:66–71. doi: 10.1111/j.1460-9568.1991.tb00812.x. [DOI] [PubMed] [Google Scholar]
  5. Bilello J. A., Pitts O. M., Hoffman P. M. Characterization of a progressive neurodegenerative disease induced by a temperature-sensitive Moloney murine leukemia virus infection. J. Virol. 1986;59:234–241. doi: 10.1128/jvi.59.2.234-241.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blondel B., Harrison G. G., Schubert M. Role of matrix protein in cytopathogenesis of vesicular stomatitis virus. J. Virol. 1990;64:1716–1725. doi: 10.1128/jvi.64.4.1716-1725.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bohn W., Rutter G., Hohenberg H., Mannweiler K., Nobis P. Involvement of actin filaments in budding of measles virus: Studies on cytoskeleton of infected cells. Virology. 1986;149:91–106. doi: 10.1016/0042-6822(86)90090-5. [DOI] [PubMed] [Google Scholar]
  8. Brait K., Fahn S., Schwarz G. A. Sporadic and familial parkinsonism and motor neuron disease. Neurology. 1973;23:990–1002. doi: 10.1212/wnl.23.9.990. [DOI] [PubMed] [Google Scholar]
  9. Cartag C. H., Plagemann P. G. W. Age-dependent poliomyelitis of mice: Expression of endogenous retrovirus correlates with cytocidal replication of lactate dehydrogenase-elevating virus in motor neurons. J. Virol. 1989;63:4362–4369. doi: 10.1128/jvi.63.10.4362-4369.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Carvalho Z. G., De Matos A. P. A., Rodrigues-Pousada C. Association of African swine fever virus with the cytoskeleton. Virus Res. 1988;11:175–192. doi: 10.1016/0168-1702(88)90042-1. [DOI] [PubMed] [Google Scholar]
  11. Dalakas M. C. New neuromuscular symptoms in patients with old poliomyelitis: A three-year follow-up study. Eur. Neurol. 1986;25:381–387. doi: 10.1159/000116038. [DOI] [PubMed] [Google Scholar]
  12. Dobson A. T., Margolis T. P., Sedarati F., Stevens J. G., Feldman L. T. A latent, nonpathogenic HSV-1 derived vector stably expresses bgalactosidase in motor neurons. Neuron. 1990;5:353–360. doi: 10.1016/0896-6273(90)90171-B. [DOI] [PubMed] [Google Scholar]
  13. Dreyer E. B., Kaiser P. K., Offermann J. T., Lipton S. A. HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists. Science. 1990;248:364–367. doi: 10.1126/science.2326646. [DOI] [PubMed] [Google Scholar]
  14. Duvoisin R. Etiology of Parkinson’s disease: Current concepts. Clin. Neuropharm. 1986;9(suppl. 1):S3–S11. [PubMed] [Google Scholar]
  15. Eaton B. T., Hyatt A. D., White J. R. Association of bluetongue virus with the cytoskeleton. Virology. 1987;157:107–116. doi: 10.1016/0042-6822(87)90319-9. [DOI] [PubMed] [Google Scholar]
  16. Eneroth A., Kristensson K., Ljungdahl Å., Olsson T. Interferon-γ-like immunoreactivity in developing rat spinal ganglia neuronin vivo andin vitro. J. Neurocytol. 1991;20:225–231. doi: 10.1007/BF01186995. [DOI] [PubMed] [Google Scholar]
  17. Fagraeus A., Tyrrell D. L. J., Norberg R., Norrby E. Actin filaments in paramyxovirus-infected human fibroblasts studied by indirect immunofluorescence. Arch. Virol. 1978;57:291–296. doi: 10.1007/BF01320068. [DOI] [PubMed] [Google Scholar]
  18. Farooqui A. A., Taylor W. A., Horrocks L. A. Phospholipases, lysophospholipases, and lipases and their involvement in various diseases. Neurochem. Pathol. 1987;7:99–128. doi: 10.1007/BF02834212. [DOI] [PubMed] [Google Scholar]
  19. Fishman P. S., Gass J. S., Swoveland P. T., Lavi E., Highkin M. K., Weiss S. R. Infection of the basal ganglia by a murine corona virus. Science. 1985;229:877–879. doi: 10.1126/science.2992088. [DOI] [PubMed] [Google Scholar]
  20. Friedland R. P., May C., Dahlberg J. The viral hypothesis of Alzheimer’s disease. Absence of antibodies to lentivituses. Arch. Neurol. 1990;47:177–177. doi: 10.1001/archneur.1990.00530020083019. [DOI] [PubMed] [Google Scholar]
  21. Gardner M. B. Retroviral spongiform polioencephalomyelopathy. Rev. Infect. Dis. 1985;7:99–110. doi: 10.1093/clinids/7.1.99. [DOI] [PubMed] [Google Scholar]
  22. Gautrin D., Gauthier S. Alzheimer’s disease: Environmental factors and etiologic hypotheses. Canad. J. Neurol. Sci. 1989;16:375–387. doi: 10.1017/s0317167100029425. [DOI] [PubMed] [Google Scholar]
  23. Ghetti B., Tagliavini F., Masters C. L., Beyreuther K., Giaccone G., Vergo L., Farlow M. R., Coneally P. M., Dlouky S. R., Ayyarelli B. Gerstmann-Sträussler-Scheinker disease: II. Neurofibrillary tangles and plaques with PrP-amyloid coexist in an affected family. Neurology. 1989;39:1453–1461. doi: 10.1212/wnl.39.11.1453. [DOI] [PubMed] [Google Scholar]
  24. Giuffre R. M., Tovell D. R., Kay C. M., Tyrell D. L. J. Evidence for an interaction between the membrane protein of paramyxovirus and actin. J. Virol. 1982;42:963–968. doi: 10.1128/jvi.42.3.963-968.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Guinea R., Carrasco L. Phospholipid biosynthesis and poliovirus genome replication, two coupled phenomena. EMBO J. 1990;9:2011–2016. doi: 10.1002/j.1460-2075.1990.tb08329.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hsiao K. K., Scott M., Foster D., Groth D., De Armond S. J., Prusiner S. B. Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science. 1990;250:1587–1590. doi: 10.1126/science.1980379. [DOI] [PubMed] [Google Scholar]
  27. Hsiao K., Prusiner S. B. Inherited human prion diseases. Neurology. 1990;40:1820–1827. doi: 10.1212/wnl.40.12.1820. [DOI] [PubMed] [Google Scholar]
  28. Huang R. T. C., Uslu G. Interplay between lipids and glycoproteins during hemolysis and fusion by influenza virus. J. Biol. Chem. 1986;261:12911–12914. [PubMed] [Google Scholar]
  29. Jerkofsky M., de Siewo A. J. Differentiation of strains of varicella zoster virus by change in neutral lipid metabolism in infected cells. J. Virol. 1986;57:809–815. doi: 10.1128/jvi.57.3.809-815.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Jones N. L., Lewis J. C., Kilpatrick B. A. Cytoskeletal disruption during human cytomegalovirus infection of human lung fibroblasts. J. Cell Biol. 1986;41:304–312. [PubMed] [Google Scholar]
  31. Kawanischi T., Akiguchi I., Fujita M., Kamegama M, Hatanaka M. Low-titer antibodies reactive with HTLV-1 gag p 19 in patients with chronic myeloneuropathy. Ann. Neurol. 1989;26:515–522. doi: 10.1002/ana.410260404. [DOI] [PubMed] [Google Scholar]
  32. Knipe D. M. Virus-host cell interactions. In: Fields B. W., Knipe D. M., editors. Fields Virology. New York: Raven; 1990. pp. 293–316. [Google Scholar]
  33. Kristensson K., Leestma J., Lundh B., Norrby E. Sendai virus infection in the mouse brain: Virus spread and long-term effects. Acta Neuropathol. 1984;63:89–95. doi: 10.1007/BF00697190. [DOI] [PubMed] [Google Scholar]
  34. Kristensson K., Norrby E. Persistence in RNA viruses in the central nervous system. In: Ornston L. N., Balows A., Baumann P., editors. Annual Review of Microbiology. Palo Alto, CA: Annual Reviews; 1986. pp. 159–184. [DOI] [PubMed] [Google Scholar]
  35. Ljungdahl Å., Olsson T., Van der Meide P. H., Holmdahl R., Klareskog L., Höjeberg B. Interferon-gamma-like immunoreactivity in certain neurons of the central and peripheral nervous sytems. J. Neurosci. Res. 1989;24:451–456. doi: 10.1002/jnr.490240316. [DOI] [PubMed] [Google Scholar]
  36. Löve A., Rydbeck R., Utter G., Örvell C., Kristensson K., Norrby E. Monoclonal antibodies against the fusion protein are protective in necrotizing mumps meningoencephalitis. J. Virol. 1986;58:220–222. doi: 10.1128/jvi.58.1.220-222.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Löve A., Andersson T., Norrby E., Kristensson K. Mumps virus infection of dissociated rodent spinal ganglia in vitro. Expression and disappearance of viral structural proteins from neurons. J. Gen. Virol. 1987;68:1755–1759. doi: 10.1099/0022-1317-68-6-1755. [DOI] [PubMed] [Google Scholar]
  38. Luftig R. B. Does the cytoskeleton play a significant role in animal virus replication? J. Theor. Biol. 1982;99:173–191. doi: 10.1016/0022-5193(82)90397-6. [DOI] [PubMed] [Google Scholar]
  39. Lundh B., Kristensson K., Norrby E. Selective infections of olfactory and respiratory epithelium by vesicular stomatitis and Sendai viruses. Neuropathol. Appl. Neurobiol. 1987;13:111–122. doi: 10.1111/j.1365-2990.1987.tb00175.x. [DOI] [PubMed] [Google Scholar]
  40. Lynn W. S., Tweedale A., Cloyd M. W. Human immunodeficiency virus (HIV-1) cytotoxicity: Perturbation of the cell membrane and depression of phospholipid synthesis. Virology. 1988;163:43–51. doi: 10.1016/0042-6822(88)90232-2. [DOI] [PubMed] [Google Scholar]
  41. Maehlen J., Wallen P., Löve A., Norrby E., Kristensson K. Paramyoxvirus infections alter certain functional properties in cultured sensory neurons. Brain Res. 1991;540:123–130. doi: 10.1016/0006-8993(91)90498-K. [DOI] [PubMed] [Google Scholar]
  42. Maehlen J., Olsson T., Löve A., Klareskog L., Norrby E., Kristensson K. Persistence of measles virus in rat brain neurons is promoted by depletion of CD8+T cells. J. Neuroimmunol. 1989;21:149–155. doi: 10.1016/0165-5728(89)90170-7. [DOI] [PubMed] [Google Scholar]
  43. Maehlen J., Daa Schröder H., Klareskog L., Olsson T., Kristensson K. Axotomy induced MHC class I antigen expression on rat nerve cells. Neurosci. Lett. 1988;92:8–13. doi: 10.1016/0304-3940(88)90733-1. [DOI] [PubMed] [Google Scholar]
  44. Malvoisin E., Wild F. Effect of drugs which inhibit cholesterol synthesis on syncytic formation in vero cells infected with measles virus. Biochim. Biophys. Acta. 1990;1042:359–364. doi: 10.1016/0005-2760(90)90165-t. [DOI] [PubMed] [Google Scholar]
  45. Mendelsohn C. L., Wimmer E., Racaniello V. R. Cellular receptor for poliovirus: Molecular cloning, nucleotide sequence and expression of a new member of the immunoglobulin superfamily. Cell. 1989;56:855–866. doi: 10.1016/0092-8674(89)90690-9. [DOI] [PubMed] [Google Scholar]
  46. Mohammed A. K., Magnusson O., Maehlen J., Fonnum F., Norrby E., Schultzberg M., Kristensson K. Behavioural deficits and serotonin depletion in adult rats after transient infant nasal viral infection. Neuroscience. 1990;35:355–363. doi: 10.1016/0306-4522(90)90089-M. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Mozar H. N., Bal D. G., Howard J. T. Perspectives on the etiology of Alzheimer’s diease. J. Am. Med. Assoc. 1987;257:1503–1507. doi: 10.1001/jama.257.11.1503. [DOI] [PubMed] [Google Scholar]
  48. Murphy C. J., Bikel I., Livingston D. M. Cellular proteins which can specifically associate with Simian virus 40 small t antigen. J. Virol. 1986;59:692–702. doi: 10.1128/jvi.59.3.692-702.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Murti K. G., Goorha R. Interaction of Frog virus 3 with the cytoskeleton. I. Altered organization of microtubules, intermediate filaments and microfilaments. J. Cell Biol. 1983;96:1248–1257. doi: 10.1083/jcb.96.5.1248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Murti K. G., Goorha R., Klymkowsky M. W. A functional role for intermediate filament in the formation of frog 3 assembly sites. Virology. 1988;162:264–269. doi: 10.1016/0042-6822(88)90420-5. [DOI] [PubMed] [Google Scholar]
  51. Norrild B., Lehto V.-P., Virtanen I. Organization of cytoskeleton elements during herpes simplex virus type 1 infection of human fibroblasts: An immunofluorescence study. J. Gen. Virol. 1986;67:97–105. doi: 10.1099/0022-1317-67-1-97. [DOI] [PubMed] [Google Scholar]
  52. Oldstone M. B. A. Molecular mimicry and autoimmune disease. Cell. 1987;50:819–819. doi: 10.1016/0092-8674(87)90507-1. [DOI] [PubMed] [Google Scholar]
  53. Olsson T., Kristensson K., Ljungdahl Å., Maehlen J., Holmdahl R., Klareskog L. Gamma-interferon-like immunoreactivity in axotomized rat motor neuron. J. Neurosci. 1989;9:3870–3875. doi: 10.1523/JNEUROSCI.09-11-03870.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Paquette Y., Kay D. G., Rassart E., Robitaille Y., Jolicoeur P. Substitution of the U3 long terminal repeat region of the neurotropic Cas-Br-E retrovirus affects its disease-inducing potential. J. Virol. 1990;64:3742–3752. doi: 10.1128/jvi.64.8.3742-3752.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Pearson R. C. A., Powell T. P. S. The neuroanatomy of Alzheimer’s disease. Rev. Neurosci. 1989;2:101–122. doi: 10.1515/REVNEURO.1989.2.2.101. [DOI] [PubMed] [Google Scholar]
  56. Pogo B. G. T., Casals J., Elizan T. S. A study of viral genomes and antigens in brains of patients with Alzheimer’s disease. Brain. 1987;110:907–915. doi: 10.1093/brain/110.4.907. [DOI] [PubMed] [Google Scholar]
  57. Prusiner S. B. Scrapie prions. Ann. Rev. Microbiol. 1989;43:345–374. doi: 10.1146/annurev.mi.43.100189.002021. [DOI] [PubMed] [Google Scholar]
  58. Ridley R. M., Baker H. F., Crow T. J. Transmissible and non-transmissible neurodegenerative disease: Similarities in age of onset and genetics in relation to aetiology. Psychol. Med. 1986;16:20–20. doi: 10.1017/S0033291700002634. [DOI] [PubMed] [Google Scholar]
  59. Roos D. S., Duchala C. S., Stephensen C. B., Holmes K. V., Choppin P. W. Control of virus-induced cell fusion by host cell lipid composition. Virology. 1990;175:345–357. doi: 10.1016/0042-6822(90)90419-R. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Sarvetnick N., Liggitt D., Pitts S. L., Hausen S. E., Stewart T. A. Insulin-dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-gamma. Cell. 1988;52:773–782. doi: 10.1016/0092-8674(88)90414-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Schimmel H., Traub P. The effect of mengovirus infection on lipid synthesis in cultured Ehrlich ascites tumour cells. Lipids. 1987;22:95–103. doi: 10.1007/BF02534860. [DOI] [PubMed] [Google Scholar]
  62. Sharpe A. H., Chen L. B., Fields B. N. The interaction of mammalian reoviruses with the cytoskeleton of monkey kidney. Virology. 1982;120:399–411. doi: 10.1016/0042-6822(82)90040-X. [DOI] [PubMed] [Google Scholar]
  63. Sharpe A. H., Hunter J. J., Chassier P., Jaenisch R. Role of abortive retroviral infection of neurons in spongiform CNS degeneration. Nature. 1990;346:181–183. doi: 10.1038/346181a0. [DOI] [PubMed] [Google Scholar]
  64. Sillevis Smitt P. A. F., de Jong J. M. B. V. Animal models of amyotropic lateral sclerosis and the spinal muscular atrophies. J. Neurol. Sci. 1989;91:231–258. doi: 10.1016/0022-510X(89)90056-7. [DOI] [PubMed] [Google Scholar]
  65. Simon K. O., Whitaker-Dowling P. A., Younger J. S., Widnell C. C. Sequential disassembly of the cytoskeleton in BHK21 cells infected with vesicular stomatitis virus. Virology. 1990;177:289–297. doi: 10.1016/0042-6822(90)90482-7. [DOI] [PubMed] [Google Scholar]
  66. Talamo B. R., Rudel R. A., Kosik K. S., Lee V. M.-Y., Neff S., Adelman L., Kauer J. Pathological changes in olfactory neurons in patients with Alzheimer’s disease. Nature. 1989;337:736–739. doi: 10.1038/337736a0. [DOI] [PubMed] [Google Scholar]
  67. Weclewicz K., Kristensson K., Örvell C. Segregation of viral structural proteins in cultured neurons of rat spinal ganglia and cord. Neuropathol. Appl. Neurobiol. 1990;16:357–364. doi: 10.1111/j.1365-2990.1990.tb01269.x. [DOI] [PubMed] [Google Scholar]
  68. Wild T. F, Bernard A., Malak N. A., Brichon G., Zuringlestein G. Imprints of virus infection: Can paramyxoviruses permanently modify triacylglycerol metabolism? Lipids. 1986;21:608–611. doi: 10.1007/BF02534060. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Chemical Neuropathology are provided here courtesy of Nature Publishing Group

RESOURCES