Slow and Persistent Viral Infections

  • Alfred S. Evans


There are two types of viral infections that bring about chronic, progressive, and usually fatal diseases involving the central nervous system (CNS). Each of them poses problems in meeting the postulates of causation thus far discussed. One type is caused by a unique group of viruses with no detectable immune response. These viruses are called “slow viruses” or “lentiviruses” because of the long period between exposure and the appearance of clinical disease, which presumably reflects the primary incubation or multiplication time for the agents. The second type of infection is caused by a group of several common and ubiquitous viruses that affect the brain several years after the primary infection and that are associated with an aberrant immune response. The two groups will be discussed separately because they require different criteria to establish a causal relationship between the virus and the disease. Certain members of the retrovirus family that bear a molecular resemblance to some of the slow viruses of animals are suspected of causing chronic infections of the CNS in humans. There are also several chronic and progressive diseases of the CNS in which a viral etiology is suspected, among which is multiple sclerosis.


Multiple Sclerosis Multiple Sclerosis Patient Progressive Multifocal Leukoencephalopathy Measle Virus Demyelinating Disease 
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. Astrom KE, Mancell EL, Richardson EP Jr: Progressive focal leukoencephalopathy. Brain 81:93–111, 1954.CrossRefGoogle Scholar
  2. Bernouilli C, Sigfried J, Baumgarten C, et al: Danger of accidental person-to-person transmission of Creutzfeldt-Jakob disease by surgery. Lancet 1:478–479, 1979.Google Scholar
  3. Brown P, Gajdusek DC: No mouse PMN leukocyte depression after inoculation with brain tissue from multiple sclerosis or spongioform encephalopathy. Nature 247:217–218, 1974.CrossRefGoogle Scholar
  4. Brown P, Tsai T, Gajdusek DC: Seroepidemiology of human papovavirus. Discovery of virgin populations and some unusual patterns of antibody prevalence among remote people of the world. Am J Epidemiol 102:331–340, 1975.Google Scholar
  5. Carp RE, Licuse PC, Merz PA, et al: Letter to editor. Multiple sclerosis-associated agent. Lancet 2:814, 1977.CrossRefGoogle Scholar
  6. Centers for Disease Control: Fatal degenerative neurological disease in patients who received pituitary-derived growth hormone. MMWR 34:359–360, 365–366, 1985.Google Scholar
  7. Centers for Disease Control: Rapidly progressive dementia in a patient who received a cadaveric dura mater graft. MMWR 36:49–50, 55, 1987.Google Scholar
  8. Centers for Disease Control: Update: Creutzfeldt-Jakob disease in a second patient who received cadaveric dura mater graft. MMWR 38:37–38, 43, 1989.Google Scholar
  9. Cook SD, Dowling PD: Multiple sclerosis and viruses: An overview. Neurology 30:80–91, 1980.CrossRefGoogle Scholar
  10. Cuille J, and Chello PL: Las “tremblante” de mouton est bien inoculable. Comptes rendus des seances de l’ Academie des Sci Paris 206:78–79, 1938.Google Scholar
  11. Gajdusek C, Zigas V: Degenerative disease of the central nervous system in New Guinea. The endemic occurrence of “kuru” in the native population. N Engl J Med 257:974, 1957.CrossRefGoogle Scholar
  12. Gajdusek DC: Kuru and Creutzfeldt-Jakob disease. Ann Clin Res 5:254, 1973.Google Scholar
  13. Gajdusek DC: Slow infections with unconventional viruses. Harvey Lect 72:283–353, 1978.Google Scholar
  14. Gajdusek DC, Gibbs CJ Jr: Subacute and chronic diseases caused by atypical infection with unconventional viruses in aberrant hosts, in Pollard M (ed): Persistent Virus Infections, Perspectives in Virology vol 8. New York, Academic Press, 1973, pp 279–301.Google Scholar
  15. Gajdusek DC, Gibbs CJ Jr, Alpers M: Experimental transmission of a kuru-like syndrome to chimpanzees. Nature 209:794–796, 1966.CrossRefGoogle Scholar
  16. Gibbs CJ Jr: Chronic neurological diseases. Subacute sclerosing panencephalitis, progressive multifocal leukoencephalopathy, kuru, Creutzfeldt-Jakob disease, in Evans AS (ed): Viral Infections of Humans: Epidemiology and Control ,3rd ed. New York, Plenum Press, 1989, pp 781–806.CrossRefGoogle Scholar
  17. Gibbs CJ Jr, Gajdusek DC, Asher DM, et al: Creutzfeldt-Jakob disease (spongioform encephalopathy): Transmission to the chimpanzee. Science 161:388–389, 1968.CrossRefGoogle Scholar
  18. Gibbs CJ Jr, Amyx WL, Bacote A, et al: Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to non-human primates. J Infect Dis 142:205–208, 1980.CrossRefGoogle Scholar
  19. Hadlow WJ: Scrapie and kuru. Lancet 2:289–290, 1959.CrossRefGoogle Scholar
  20. Henle G, Henle W, Koldovsky P, et al: Multiple sclerosis-associated agent: Neutralization of the agent by human sera. Infect Immun 12:1367–1374, 1975.Google Scholar
  21. Johnson RT: Viral Infections of the Nervous System. New York, Raven Press, 1982.Google Scholar
  22. Johnson R, Gibbs CJ Jr: Editorial. Koch’s postulates and slow infections of the nervous system. Arch Neurol 30:36–38, 1974.CrossRefGoogle Scholar
  23. Klitzman RL, Alpers MP, Gajdusek DC: The natural incubation period of kuru and the episodes of transmission in three clusters of patients. Neuroepidemiology 3:3–20, 1984.CrossRefGoogle Scholar
  24. Koldovsky U, Koldovsky P, Henle G, et al: Studies on a multiple sclerosis-associated agent-Transmission to animals and some properties of the agent. Infect Immun 12:1355–1366, 1975.Google Scholar
  25. Koprowski H, DeFreiltas EC, Harper ME, et al: Multiple sclerosis and human T-cell lymphotropic retrovirus. Nature 318:154–160, 1985.CrossRefGoogle Scholar
  26. Krupp LB, Lipton RB, Swerlow ML, et al: Progressive multifocal leukoencephalopathy: Clinical and radiologic features. Ann Neurol 17:244–349, 1985.CrossRefGoogle Scholar
  27. Kurtzke JF: Epidemiologic contributions to multiple sclerosis. An overview. Neurology 30:61–79, 1980.CrossRefGoogle Scholar
  28. Kurtzke JF: Multiple sclerosis in the Faroe Islands. III. An alternative assessment of the three epidemics. Act Neurol Scand 76:317–319, 1987.CrossRefGoogle Scholar
  29. Kurtzke JF, Hyllested K: Multiple sclerosis in the Faroe Islands: I. Clinical and epidemiological features. Ann Neurol 5:6–21, 1979.CrossRefGoogle Scholar
  30. Kurtzke JF, Hyllested K: Multiple sclerosis in the Faroe Islands: II. Clinical update, transmission, and the nature of MS. Neurology 35:672–676, 1985.CrossRefGoogle Scholar
  31. Kurtzke JF, Hyllested K: MS epidemiology in the Faroe Islands. Rev Neurol 57:77–87, 1987.Google Scholar
  32. Kurtzke JF, Priester WA: Dogs, distemper, and multiple sclerosis in the United States. Acta Neurol Scand 60:313–319, 1979.CrossRefGoogle Scholar
  33. Lang W, Miklossy J, Deranz JP, et al: Neuropathology of the acquired immunodeficiency syndrome (AIDS). Report of 135 consecutive autopsy cases from Switzerland. Acta Neuropath 77:379– 380, 1989.CrossRefGoogle Scholar
  34. London WT, Houff SA, Madden DL, et al: Brain tumors in owl monkeys with polyoma virus (JE virus). Science 201:1246–1249, 1978.CrossRefGoogle Scholar
  35. Manuelides EE, Gorgacz EJ, Manuelides L: Interspecies transmission of Creutzfeldt-Jakob disease to the Syrian hamster with reference to clinical syndromes and strains of agent. Proc Natl Acad Sci USA 75:3432–3436, 1976a.CrossRefGoogle Scholar
  36. Manuelides EE, Kim J, Angelo JN, et al: Serial propagation of Creutzfeldt-Jakob disease in guinea pigs. Proc Natl Acad Sci USA 73:223–227, 1976b.CrossRefGoogle Scholar
  37. Manuelides EE, Angelo JN, Gorgacz EJ, et al: Experimental Creutzfeldt-Jakob disease transmitted via the eye with infected cornea. N Engl J Med 296:1334–1336, 1977.CrossRefGoogle Scholar
  38. Manuelides EE, Manuelides L, Pincus JH, et al: Transmission from man to the hamster of Creutzfeldt-Jakob disease with clinical recovery. Lancet 2:40–42, 1978.CrossRefGoogle Scholar
  39. Melnick JL: Has the virus of multiple sclerosis been isolated? Yale J Biol Med 55:251–257, 1982.Google Scholar
  40. Melnick JL, Seide EL, Inoue YK, et al: Isolation of virus from spinal fluid of three patients with multiple sclerosis and one with amyotropic lateral sclerosis. Lancet 1:30–33, 1982.Google Scholar
  41. Micheletti R, Lange LS, Jakob JP, et al: Failure to isolate a transmissible agent from the bone marrow of patients with multiple sclerosis. Lancet 2:415–416, 1979.Google Scholar
  42. Mitchell DN, Porterfield JS, Micheletti R, et al: Isolation of an infectious agent from bone marrow of patients with multiple sclerosis. Lancet 2:387–391, 1978.CrossRefGoogle Scholar
  43. Mitchell DN, Goswami KK, Taylor P, et al: Failure to isolate a transmissible agent from the bone marrow of patients with multiple sclerosis. Lancet 2:415–416, 1979.Google Scholar
  44. Nathanson N, Miller A: Epidemiology of multiple sclerosis. Critique of the evidence for a viral etiology. Am J Epidemiol 107:451–461, 1978.Google Scholar
  45. Norrby E: Viral antibodies in multiple sclerosis. Prog Med Virol 24:1–39, 1978.Google Scholar
  46. Norrby E, Vankid B: Measles and multiple sclerosis. Proc R Soc Med 67:1129–1132, 1974.Google Scholar
  47. Padgett BL, Walker DL: Prevalence of antibodies in human sera against JC virus, an isolate from a case of progressive multifocal leukoencephalopathy. J Infect Dis 127:467–470, 1973.CrossRefGoogle Scholar
  48. Padgett BL, Zu Rhein GM, Walker DL, et al: Cultivation of papova-like virus from human brain with progressive multifocal leukencephalopathy. Lancet 1:1257–1260, 1971.CrossRefGoogle Scholar
  49. Panum PL: Observations Made during the Epidemic of Measles in the Faroe Islands in the Year 1846. New York, American Public Health Association, 1948.Google Scholar
  50. Prusinger SB: Novel proteinaceous infectious particles cause scrapie. Science 216:136–144, 1982.CrossRefGoogle Scholar
  51. Prusinger SB, McKinley MP, Bowman KA, et al: Scrapie prions aggregate to form amyloid-like birefrigent rods. Cell 35:349–358, 1983.CrossRefGoogle Scholar
  52. Prusinger SB: Molecular biology and genetics of neurodegenerative diseases caused by prions. Adv Virus Res 41:241–380, 1992.CrossRefGoogle Scholar
  53. Salmi A, Arnadottir T, Reulnanen et al: The significance of antibody synthesis in the central nervous system of multiple sclerosis patients, in Mims CA, Cruzner ML, Kelly RE (eds): Viruses and Demyelinating Diseases. New York, Academic Press, 1983a, pp 141–154.Google Scholar
  54. Salmi A, Reunanen M, Leonen J, et al: Intrathecal antibody synthesis to virus antigens in multiple sclerosis. Clin Exp Immunol 52:239–241, 1983b.Google Scholar
  55. Sigurdsson B: Observation on three slow infections of sheep. Br Med J 110:255, 307, 341, 1954.Google Scholar
  56. Sigurdsson B, Palsson PA, Grimsson H: Visna, a demyelinating transmissible disease of sheep. J Neuropathol Exp Neurol 15:389–403, 1957.Google Scholar
  57. Stephenson JR, ter Meulen V, Kiessling W: Search for canine distemper virus antibodies in multiple sclerosis. A detailed virological evaluation. Lancet 2:772–775, 1980.CrossRefGoogle Scholar
  58. Stoner GL: Implications of progressive multifocal leukoencephalopathy and JC virus for the etiology of MS. Acta Neurol Scand 83:20–33, 1991.CrossRefGoogle Scholar
  59. Telente A, et al: Detection of JC virus by polymerase chain reaction in cerebrospinal fluid from two patients with progressive multifocal leukoencephalopathy. Eur J Clin Microbiol Infect Dis 11:253–254, 1992.CrossRefGoogle Scholar
  60. Waksman BH: Current trends in multiple sclerosis research. Immunol Today 87–93, 1981.Google Scholar
  61. Waksman BH: Viruses and immune events in the pathogenesis of multiple sclerosis, in Mims CA, Cruzner ML, Kelly RE (eds): Viruses and Demyelinating Diseases. New York, Academic Press, 1983, pp 155–165.Google Scholar
  62. Waksman BH, Reynolds WE: Multiple sclerosis as a disease of immune regulation. Proc Soc Exp Biol Med 175:282–294, 1984.Google Scholar
  63. Walker DL, Padgett BL, Zu Rhein GM, et al: Human parvovirus (JC): Induction of brain tumors in hamsters. Science 181:674–676, 1973.CrossRefGoogle Scholar
  64. White FA, Ishaq M, Stoner GL, et al: JC virus DNA is present in many human brain samples from patients without progressive multifocal leukencephalopathy. J Virol 66:5726–5734, 1992.Google Scholar
  65. Zu Rhein GM: Association of papova-virions with a human demyelinating disease (multiple focal leukencephalopathy), Prog Med Virol 11:185–247, 1969.Google Scholar
  66. Zu Rhein GM, Chow SM: Particles resembling papovavirus in human demyelinating disease. Science 148:1477–1479, 1965.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Alfred S. Evans
    • 1
  1. 1.Yale UniversityNew HavenUSA

Personalised recommendations