Neurochemical Effects of Viral Infections in the Central Nervous System

  • K. W. Rammohan
  • A. A. Farooqui
  • L. A. Horrocks


In recent years it has become apparent that dysfunction of virus-infected cells occurs by a variety of mechanisms. Cells can harbor viruses and be unaffected, with regard to vital functions of cell division or cell differentiation. Similarly, virus persistence has been observed in vivo in the absence of any clinical illness, and these observations collectively raise the question as to what leads to cellular dysfunction in the course of a viral infection. Correlations of changes in specific molecular events to alterations in cellular function have recently been studied in a number of viral infections. Although a complete review of all viral systems studied in this regard is beyond the scope of this review, basic mechanisms highlighted by specific viral infections will be discussed such that many mechanisms by which viruses cause central nervous system (CNS) dysfunction will become evident.


Rabies Virus Measle Virus Semliki Forest Virus Glycosyl Transferase Neurochemical Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Allen, I. V. 1983, Hydrolytic enzymes in multiple sclerosis, in: Progress in Neuropathology, Volume 5, ( H. M. Zimmerman, ed.), Raven Press, New York, pp. 1–17.Google Scholar
  2. Anderton, P., Wild, T. F., and Zwingelstein, G., 1983, Measles-virus-persistent infection in BGM cell, Biochem. J. 214: 665–670.Google Scholar
  3. Annuziata, P., and Federio, A., 1981, Brain glycosidases in Creutzfeldt-Jakob disease, J. Neurol. Sci. 49: 325–328.CrossRefGoogle Scholar
  4. Aprille, J. R., Austin, J., Costello, C. E., and Royal, N., 1980, Identification of the Reye’s syndrome “serum factor”, Biochem. Biophys. Res. Commun. 94: 381–389.CrossRefGoogle Scholar
  5. Bass, N. H., Hess, H. H., and Pope, A., 1974, Altered cell membranes in Creutzfeldt-Jakob disease, Arch. Neurol. 31: 174–182.Google Scholar
  6. Bonailla, E., Ryder, S., and Hernandez, H., 1975, Venezuelan equine encephalomyelitis virus in- fection: Effect on monoamine metabolism of mouse brain, J. Neurochem. 25: 529–530.CrossRefGoogle Scholar
  7. Bowen, D. M., Flack, R. H. A., Martin, R. O., Smith, C. B., White, P., and Davison, A. N., 1974, Biochemical studies on degenerative neurological disorders. 1-Acute experimental encephalitis, J. Neurochem. 22: 1099–1107.PubMedCrossRefGoogle Scholar
  8. Bradel, E. J., and Reiner, C. B., 1975, The fine structure of hepatocvtes in Reye’s syndrome, in: Reye’s syndrome ( J. D. Pollack, ed.), Grune and Stratton, New York, pp. 147–158.Google Scholar
  9. Brown, R. E., and Madge, G. E., 1972, Fatty acids and mitochondrial injury in Reye’s syndrome, N. Engl. J. Med. 286: 787–788.PubMedCrossRefGoogle Scholar
  10. Chan, P. H., Fishman, R. A., Lei, J. L., and Quan, S. C., 1980, Arachidonic acid induced swelling in uncirbated rat brain slices, Neurochem. Res. 5: 629–639.Google Scholar
  11. Clowes, A. W., Cherry, R. J., and Chapman, D.. 1972, Physical effects of tetanus toxin on model membranes containing ganglioside, J. Mol. Biol. 67: 49–57.PubMedCrossRefGoogle Scholar
  12. Craighead, J. E., 1975, The role of viruses in the pathogenesis of pancreatic disease and diabetes mellitis, Prog. Med. Virol. 19: 162–207.Google Scholar
  13. deDuve, C., 1978, A reexamination of the physiological role of peroxisomes, in: Tocopherol. Oxygen and Biomembrane ( C. deDuve and O. Hayaishi, eds.), Elsevier, Amsterdam, pp. 351–361.Google Scholar
  14. De Vivo, D. C., and Keating, J. P., 1976, Reye’s syndrome, Adv. Pediatr. 22: 175–230.Google Scholar
  15. Doyle, L. B., Doyle, M. V., and Oldstone, M. B. A., 1980, Susceptibility of newborn mice with H 2k background to lymphocytic choriomeningitis virus infection, Immunology 40: 589–596.PubMedGoogle Scholar
  16. Dubois-Dalcq, M., Hooghe-Peters, E. L., and Lazzarim, R. A., 1980, Antibody-induced modulation of rhabdovius infection of neurons in vitro, J. Neuropathol. Exp. Neurol. 39: 507–522.PubMedCrossRefGoogle Scholar
  17. Fernandez-Puentes, G., 1983, Permeability of alpha sarcin virus-infected cells, Mol. Cell. Biochem. 50: 185–191.CrossRefGoogle Scholar
  18. Fishman, P. H., and Brady, R. O., 1976, Biosynthesis and function of ganglioside, Science 194: 906–915.PubMedCrossRefGoogle Scholar
  19. Friede, R. L., and DeJong. R. N., 1964, Neuronal enzymatic failure in Creutzfeldt-Jakob disease, Arch. Neurol. 10: 181–195.Google Scholar
  20. Goudsmit, J.. Rohwer, R. G., Silbergeld, E. K., and Gadjusek, D. C., 1981, Hypersensitivity to central serotonin receptor activation in scrapie-infected hamsters and the effect of serotonergic drugs on scrapie symptoms, Brain Res. 220: 372–377.Google Scholar
  21. Greenstein, J. I., Baron-Van Evercooren, A., Lazzarini, R. A., and McFarland, H. F., 1981, Infection of the central nervous system produced by the R1 vesicular stomatitis virus, Lab. Invest. 44: 487–495.Google Scholar
  22. Haig, D. A., and Clarke, M. C., 1971, Multiplication of the scrapie agent, Nature (London) 234: 106–107.CrossRefGoogle Scholar
  23. Hakamori, S., 1973, Glycolipids of tumor cell surface, Adv. Cancer Res. 18: 265–315.CrossRefGoogle Scholar
  24. Halbach, M.. and Koschel, K., 1979, Impairment of hormone dependent signal transfer by chronic SSPE virus infection, J. Gen. Virol. 42: 615–619.PubMedCrossRefGoogle Scholar
  25. Hamberger, A., and Svennerholm, L., 1971, Composition of gangliosides and phospholipids of neuronal and glial cell enriched fractions, J. Neurochem. 18: 1821–1829.PubMedCrossRefGoogle Scholar
  26. Haspel, M. V., Onodera, T., Prabhakar, B. X., Horita, M., Suzuki, H., and Notkins, A. L., 1983, Virus-induced autoimmunity: Monoclonal antibodies that react with endocrine tissue, Science 220: 304–306.PubMedCrossRefGoogle Scholar
  27. Horrocks, L. A., Spanner, S., Mozzi, R., Fu, S. C., D’Amato, R. A., and Krakowka, S., 1978, Plasmologenase is elevated in early demyelinating lesions, Adv. Exp. Biol. Med. 100: 423–438.Google Scholar
  28. Huang, A. S., and Wagner, R. R., 1965, Inhibition of cellular RNA synthesis by nonreplicating vesicular stomatitis virus, Proc. Natl. Acad. Sci. U.S.A. 54: 1579–1582.PubMedCrossRefGoogle Scholar
  29. Jurkowitz, M., Scott, K. M., Altshuld, R. A., Merola, A. J., and Brierley, G. P., 1974, Retention and loss of energy coupling in aged heart mitochondria, Arch. Biochem. Biophys. 165: 98–113.CrossRefGoogle Scholar
  30. Knobler, R. L., Dubois-Dalcq, M., Haspel, M. V., Clay Smith, A. P., Lampert, P. W., and Oldstone, M. B. A., 1981, Selective localization of wild type and mutant mouse hepatitis virus OHM Strain) antigens in CNS tissue by fluorescence, light and electron microscopy, J. Neuroimmunol. 1: 81–92.PubMedCrossRefGoogle Scholar
  31. Kontos, H. A., Wei, E. P., Povlishock, J. T., Dietrick, W. D., Magiera, C. J., and Ellis, E. F., 1980, Cerebral arteriolar damage by arachidonic acid and prostaglandin G-2, Science 209: 1242–1244.PubMedCrossRefGoogle Scholar
  32. Lai, C. S., and Piette, L. M., 1977, Hydroxyl radical production involved in lipid peroxidation of rat liver microsomes, Biochem. Biophys. Res. Commun. 78: 51–59.CrossRefGoogle Scholar
  33. Lai, C. S., and Piette, L. M., 1978, Spin-trapping studies of hydroxyl radical production involved in lipid peroxidation, Arch. Biochem. Biophys. 190: 27–38.CrossRefGoogle Scholar
  34. Lampert, P., Hooks, J., Gibbs, J. R., C. J., and Gajdusek, D. C., 1971, Altered plasma membranes in experimental scrapie, Acta Neuropathol. 19: 81–93.Google Scholar
  35. Lentz, T. L., Burrage, T. A., Smith, A. L., Crick, J., and Tignor, G. H., 1982, Is the acetylcholine receptor a rabies virus receptor, Science 215: 182–184.PubMedCrossRefGoogle Scholar
  36. Levitt, M., Spector, S., Sjoerdsma, A., and Udenfriend, S., 1965, Elucidation of the rate-limiting step in norepinephrine biosynthesis in the perfused guinea-pig heart, J. Pharmacol. Exp. Ther. 148: 1–8.PubMedGoogle Scholar
  37. Lotscher, H., Winterhalter, K. H., Carafoli, E., and Richter, C., 1979, Hydroperoxide can modulate the redox state of pyridine nucleotides and calcium balance in rat liver mitochondria, Proc. Natl. Acad. Sci. U.S.A. 76: 4340–4344.PubMedCrossRefGoogle Scholar
  38. Lotscher, H., Winterhalter, K. H., Carafoli, E., and Richter, C., 1980, Hydroperoxide induced loss of pyridine nucleotides and release of calcium from rat liver mitochondria, J. Biol. Chem. 255: 9325–9330.PubMedGoogle Scholar
  39. Lycke, E., and Roos, B. E., 1968, Effect on the monoamine-metabolism of the mouse brain by experimental Herpes simplex infection, Experientia 24: 687–689.PubMedCrossRefGoogle Scholar
  40. Lycke, E., and Roos, B. E., 1972, The monoamine metabolism in viral encephalitides of the mouse II. Turnover of monoamines in mice infected with Herpes simplex virus, Brain Res. 44:603– 613.Google Scholar
  41. Lycke, E., Modigh, K., and Roos, B. E., 1970, The monoamine metabolism in viral encephalitides of the mouse 1. Virological and biochemical results, Brain Res. 23: 235–246.PubMedCrossRefGoogle Scholar
  42. Manunes, P., DeVries, G., Miller, H., and David, R. B.. 1974, Fatty acids in Reye’s syndrome, Pediatr. Res. 8: 436.Google Scholar
  43. Martin, F. J., and MacDonald, R. C., 1976, Phospholipid exchange between bilayer membrane vesicles, Biochemistry 15: 321–327.PubMedCrossRefGoogle Scholar
  44. McMartin, D. N., Koestner, A., and Long, J. F., 1972, Enzyme activities associated with the demvelinating phase of canine distemper, Acta Neuropathol. 22: 275–287.PubMedCrossRefGoogle Scholar
  45. Millson, G. C., and Bountiff, L., 1973, Glycosidases in normal and scrapie mouse brain, J. Neurochem. 20: 541–546.PubMedCrossRefGoogle Scholar
  46. Moller, G., 1981, MHC restriction of antiviral immunity, Immunol. Rev. 58: 5–157.Google Scholar
  47. Morell, P., Bornstein, M. R., and Norton, W. T., 1972, Diseases of myelin, in: Basic Neurochemistry ( R. Albers, G. J. Siegel, R. Katzman, and B. W. Agranoff, eds.) Little Brown and Co., Boston, p. 497–516.Google Scholar
  48. Munzel, P., and Koschel, K., 1982, Alteration in phospholipid methylation and impairment of signal transmission in persistently paramyrovirus-infected rat glioma cells, Proc. Natl. Acad. Sci. U.S.A. 79: 3692–3696.PubMedCrossRefGoogle Scholar
  49. Norton, W. T., Poduslo, S. E., and Suzuki, K., 1966, Subacute sclerosing leukoencephalitis. II. Chemical studies including abnormal myelin and abnormal ganglioside pattern, J. Neuropathol. Exp. Neurol. 25: 582–590.PubMedCrossRefGoogle Scholar
  50. Norton, W. T., Abe, T., Poduslo, S. E., and DeVries, G. H., 1975, The lipid composition of isolated brain cells and axons, J. Neurosci. Res. 1: 57–75.PubMedCrossRefGoogle Scholar
  51. Ogburn, P. L., Sharp, H., Lloyd-Still, J. D., Johnston, S. B., and Holman, R. T., 1982, Abnormal polyunsaturated fatty acid patterns of serum lipids in Reye’s syndrome, Proc. Natl. Acad. Sci. U.S.A. 79: 908–911.PubMedCrossRefGoogle Scholar
  52. Oldstone, M. B. A., Holmstoen, J., and Walsh, R. M., 1977, Alterations of acetylcholine enzymes in neuroblastoma cells persistently infected with lymphocytic choriomeningitis virus, J. Cell. Physiol. 91: 459–472.PubMedCrossRefGoogle Scholar
  53. Oldstone, M. B. A., Sinha, Y. N., Blount, P., Tishon, A., Rodriquez, M., Wedel, R. V., and Lampert, P. W., 1982, Virus-induced alterations in homeostasis: Alterations in differentiated functions of infected cells in vivo, Science 218: 1125–1127.PubMedCrossRefGoogle Scholar
  54. Onodera, T., Toniolo, A., Ray, U. R., Jenson, A. B., Knazek, R. A., and Notkins, A. L., 1981, Virus-induced diabetes mellitus: Polyendocrinopathy and autoimmunity, J. Exp. Med. 153: 1457–1473.PubMedCrossRefGoogle Scholar
  55. Osmundsen, H., Neat, C. E., and Norum, K. R., 1979, Peroxisomal oxidation of long chain fatty acids, FEBS Lett. 909: 292–296.CrossRefGoogle Scholar
  56. Papahadjopoulos, D., Vail, W. J., Newton, C., Nir, S., Jacobson, K., Poste, G., and Lazo, R., 1977, Studies on menbrane fusion III. The role of calcium-induced phase changes, Biochim. Biophys. Acta 465: 579–598.CrossRefGoogle Scholar
  57. Partin, J. C., Bove, K., Partin, J. S., and Schubert, K., 1979, Liver and muscle ultrastructure in Reye’s syndrome, in: Reye’s Syndrome ( J. F. S. Crocker, ed.), Grune and Stratton, New York, pp. 217–201.Google Scholar
  58. Pennington, S. N., and Smith, C. T., 1978, Indomethacin stimulation of lipid peroxidation and chemiluminescence in rat liver microsomes, Lipids 13: 636–643.PubMedCrossRefGoogle Scholar
  59. Pollack, J. D., Cramblett, H. G., Flynn, D., and Clark, D., 1975, Serum and tissue lipids in Reye’s syndrome, in: Reye’s Syndrome ( J. D. Pollack, ed.), Grune and Stratton, New York, pp. 227–243.Google Scholar
  60. Pope, A., Hess, H. H., and Lewin, E., 1964, Microchemical pathology of the cerebral cortex in presenile dementias, Trans. Am. Neurol. Assoc. 89: 15.Google Scholar
  61. Pottelsberghe, C. V., Rammohan, K. W., McFarland, H. F., and Dubois-Dalcq, M., 1979, Selective neuronal, dendritic, and postsynaptic localization of viral antigen in measles-infected mice, Lab. Invest. 40: 99–108.Google Scholar
  62. Reye, R. D. C., Morgan, G., and Baral, J., 1963, Encephalopathy and fatty degeneration of the viscera, Lancet 2: 749–752.PubMedCrossRefGoogle Scholar
  63. Richardson, C. L., Baker, S. R., Morre, D. J., and Keena, T. W., 1975, Glycosphingolipid synthesis and tumorigenesis, Biochim. Biophys. Acta 417: 175–186.Google Scholar
  64. Riviere, Y., Gressor, I., Guillon, J. C., Bandu, M. T., Ronco, P., Morel-Maroger, L., and Verroust, P., 1980, Severity of lymphocytic choriomeningitis virus disease in different strains of suckling mice correlates with increasing amounts of endogenous interferon, J. Exp. Med. 152: 633–640.PubMedCrossRefGoogle Scholar
  65. Rohwer, R. G., Neckers, L. M., Trepel, J. B., Gajdusek, C. D., and Wyatt, R. J., 1981, Serotonin concentrations in brain and blood of scrapie infected and normal hamsters and mice, Brain Res. 220: 367–371.PubMedCrossRefGoogle Scholar
  66. Rutter, G., Asher, D. M., Rohwer, R. G., Gibbs, Jr., C. J., and Gadjusek, D. C., 1981, Increased concanavalin A capping in cells from brains of scrapie-infected hamsters, Arch. Virol. 68: 129–133.Google Scholar
  67. Suckling A. J., and Hunter, G. D., 1974 Glycosyl transferase activity in normal and scrapie-affected mouse brain, J. Neurochem. 22: 1005–1012.PubMedCrossRefGoogle Scholar
  68. Suzuki, K., and Chen, G., 1966, Chemical studies on Jakob-Creutzfeldt disease, J. Neuropathol. Exp. Neurol. 15: 396–408.CrossRefGoogle Scholar
  69. Suzuki, Y., and Matsumoto, M., 1982, Release of lysosomal phospholipase AI and Az into cytosol and rapid turnover of newly-formed lysophosphaticlylcholine in FL cells during fusion from within induced by measles virus, J. Biochem. (Tokyo) 92: 1683–1692.Google Scholar
  70. Tamai, Y., Kojima, H., Ikuta, I., and Kumanishi, T., 1978, Alteration in the composition of brain lipids in patients with Creutzfeldt-Jacob disease, J. Neurol. Sci. 35: 59–76.PubMedCrossRefGoogle Scholar
  71. Trauner, D. A., 1982, Reye’s syndrome, Trends Neurosci. 5: 131–133.CrossRefGoogle Scholar
  72. Trauner, D. A., and Adams, H., 1981, Intracranial pressure elevations during octanoate infusion in rabbits: An experimental model of Reye’s syndrome, Pediotr. Bes. 15: 1097–1199.Google Scholar
  73. Trauner, D. A., Nyhan, W. L., and Sweetman, L., 1975, Short chain organic acidemia and Reye’s syndrome, Neurology 25: 290–293.Google Scholar
  74. Tubaro, E., Lotti, B., Cavallo, G., Croce, C., and Borelli, G., 1980, Liver xanthine oxidase increase in mice in three pathological models, Biochem. Pharamacol. 29: 1939–1943.CrossRefGoogle Scholar
  75. Viret, J., Dormont, D., Molle, D., Court, L., Leterrier, F., Cathala, F., Gibbs, Jr., C. J., and Gadjusek, D. C., 1981, Structural modifications of nerve membranes during experimental scrapie evolution in mouse, Biochem. Biophys. Bes. Commun. 101: 830–836.CrossRefGoogle Scholar
  76. Weiner, L. P., Johnson, R. T., and Hemden, R. N., 1973, Viral infection and demyelinating disease. N. Engl. J. Med. 288: 1102–1105.CrossRefGoogle Scholar
  77. Yoon, J. W., Austin, M., Onodera, T., and Notkins, A. L., 1979, Virus-induced diabetes mellitus: Isolation of a virus from the pancreas of a child with diabetic ketoacidosis, N. Engl. J. Med. 300: 1173–1179.PubMedCrossRefGoogle Scholar
  78. Yu, R. K., and Manuelidis, E. E., 1976, Ganglioside alterations in guinea pig brains at end stages of experimental Creutzfeldt-Jakob disease, J. Neurol. Sci. 35: 15–23.CrossRefGoogle Scholar
  79. Yu, R. K., Ledeen, R. W., Gadjusek, D. C., and Gibbs, C. J, 1974, Ganglioside changes in slow virus disease: Analysis of chimpanzee brains affected with Kuru and Creutzfeldt-Jakob agents, Brain Res. 70: 103–112.PubMedCrossRefGoogle Scholar
  80. Zieve, R. J., Zieve, L. Y., Doizaki. W. M., and Gilsdorf, R. B., 1974, Synergism between ammonia and fatty acids in the production of coma: Implication for hepatic coma, J. Pharmocol. Exp. Ther. 191: 19–26.Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • K. W. Rammohan
    • 1
  • A. A. Farooqui
    • 2
  • L. A. Horrocks
    • 2
  1. 1.Department of NeurologyOhio State UniversityColumbusUSA
  2. 2.Department of Physiological ChemistryOhio State UniversityColumbusUSA

Personalised recommendations