Pathogenesis of Age-Dependent Poliomyelitis of Mice

Viral and Immunological Factors Contributing to Fatal Paralysis
  • Christopher H. Contag
  • John T. Harty
  • Peter G. W. Plagemann


Lactate dehydrogenase-elevating virus (LDV) is a generally nonpathogenic mouse virus (for reviews see refs. 1, 2, 3, 4, 5). LDV infections in most strains of Mus musculus usually result in lifelong, persistent, asymptomatic infections. However, in highly leukemic strains of mice, peripheral inoculations of LDV can result in a fatal paralytic disease (6, 7) that has been shown to involve direct cytopathic effects of LDV infections on motor neurons (see Section 3. ). LDV infection of motor neurons is dependent on the expression of an endogenous, ecotropic murine leukemia virus (MLV) in these cells (see Section 4. ). Susceptibility in genetically predisposed strains of mice is related to the age of the animals at the time of LDV infection (6, 7, 8); hence, the neurological disease is referred to as age-dependent poliomyelitis (ADPM). The age at which mice become susceptible can be modulated by immunosuppressive agents, such as cyclophosphamide and X-irradiation (6, 7, 9, 20). In addition to the genetic and viral factors involved in the development of ADPM, humoral and cellular immune functions appear to control both the initiation and the progression of the neurological disease caused by LDV (see Section 5. ).


Spinal Cord Motor Neuron Murine Leukemia Virus Nonneuronal Cell Equine Arteritis Virus 
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  1. 1.
    Cafruny, W. A. (1989) Lactate dehydrogenase-elevating virus: Biology and pathogenesis. Crit. Rev. Microbiol. 17, 107–119.PubMedGoogle Scholar
  2. 2.
    Notkins, A. L. (1965) Lactic dehydrogenase virus. Bad. Rev. 29, 143–160.Google Scholar
  3. 3.
    Riley, V. (1974) Persistence and other characteristics of the lactate dehydrogenase-elevating virus (LDH-virus). Prog. Med. Virol. 18, 198–213.PubMedGoogle Scholar
  4. 4.
    Rowson, K. E. K. and B. W. J. Mahy (1975) Lactate dehydrogenase virus, in Virology Monographs, vol. 13. Springer-Verlag, New York.Google Scholar
  5. 5.
    Rowson, K. E. K. and B. W. J. Mahy (1985) Lactate dehydrogenase-elevating virus. J. Gen. Virol. 66, 2297–2312.PubMedGoogle Scholar
  6. 6.
    Murphy, W. H., J. F. Nawrocki, and L. R. Pease (1983) Age-dependent paralytic viral infection in C58 mice: Possible implications in human neurological disease. Progr. Brain Res. 59, 291–303.Google Scholar
  7. 7.
    Murphy, W. H., J. J. Mazur, and S. A. Fulton (1987) Animal model of motor neuron disease, in Clinical Neuroimmunology. W. M. H. Behan, P. O. Behan, and J. A. Aarli, eds. Blackwell Scientific, Oxford, pp. 135–155.Google Scholar
  8. 8.
    Pease, L. R. and W. H. Murphy (1980) Co-infection by lactate dehydrogenase virus and C-type retrovirus elicits neurological disease. Nature 286, 398–400.PubMedGoogle Scholar
  9. 9.
    Contag, C. H., J. T. Harty, and P. G. W. Plagemann (1989) Dual virus etiology of age-dependent poliomyelitis of mice. A potential model for human motor neuron disease. Microb. Pathogen. 6, 391–401.Google Scholar
  10. 10.
    Plagemann, P. G. W. and V. Moennig (1992) Lactate dehydrogenase-elevating virus, equine arteritis virus and simian hemorrhagic fever virus. A new group of positive strand RNA viruses. Adv. Virus Res. in press.Google Scholar
  11. 11.
    Brinton, M. (1980) Non-arbo-togaviruses. Lactate dehyrogenase-elevating virus, in The Togaviruses. Biology, Structure and Replication. R. W. Schlesinger, ed. Academic, New York, pp. 623–666.Google Scholar
  12. 12.
    Brinton-Darnell, M. and P. G. W. Plagemann (1975) Structure and chemical-physical characteristics of lactate dehydrogenase-elevating virus. J. Virol. 16, 420–433.PubMedGoogle Scholar
  13. 13.
    Westaway, E. G., M. A. Brinton, S. Y. Gaidamovich, M. C. Horzinek, A. Igarashi, L. Kääriäinen, D. K. Lvov, J. S. Porterfield, P. K. Russel, and D. W. Trent (1985) Togaviridae. Intervirology 24, 125–139.PubMedGoogle Scholar
  14. 14.
    Horzinek, M. C., P. S. van Wielink, and D. J. Ellens (1975) Purification and electron microscopy of lactate dehydrogenase virus of mice. J. Gen. Virol 26, 217–226.PubMedGoogle Scholar
  15. 15.
    Michaelides, M. C. and S. Schlesinger (1973) Structural proteins of lactate dehydrogenase-elevating virus. Virology 55, 211–217.PubMedGoogle Scholar
  16. 16.
    Cafruny, W. A., S. P. K. Chan, J. T. Harty, S. Yousefi, K. Kowalchyk, D. McDonald, B. Foreman, G. Budweg, and P. G. W. Plagemann (1986) Antibody response of mice to lactate dehyhrogenase-elevating virus during infection and immunization with inactivated virus. Virus Res. 5, 357–375.PubMedGoogle Scholar
  17. 17.
    Godeny, E. K., M. R. Werner, and M. A. Brinton (1989) The 3′ terminus of lactate dehydrogenase-elevating virus genome RNA does not contain togavirus or flavivirus conserved sequences. Virology 172, 647–650.PubMedGoogle Scholar
  18. 18.
    Godeny, E. K., D. W. Speicher, and M. A. Brinton (1990) Map location of lactate dehydrogenase-elevating virus (LDV) capsid (Vp1) gene. Virology 177, 768–771.PubMedGoogle Scholar
  19. 19.
    Kuo, L., J. T. Harty, L. Erickson, G. Palmer, and P. G. W. Plagemann (1991) A nested set of eight RNAs formed in macrophages infected with lactate dehydrogenase-elevating virus. J. Virol. 65(9), 5118–5123.PubMedGoogle Scholar
  20. 20.
    de Varies, A. A., E. D. Chrinside, P. J. Bredenbeck, L. A. Gravestein, M. C. Horzinek, and W. J. M. Spaan (1990) All subgenomic mRNAs of equine arteritis 27 virus contain a common leader sequence. Nucleic Acid Res. 18, 3241–3247.Google Scholar
  21. 21.
    Spaan, W. J. M., J. A. den Boon, P. J. Bredenbeck, E. D. Chirnside, A. G. H. Noten, E. J. Snijder, A. A. F. de Vries, and M. C. Horzinek (1990) Comparative and evolutionary aspects of coronaviral, arteriviral and toroviral genome structure and expression, in New Aspets of Positive Strand RNA Viruses. M. A. Brinton and F. X. Heinz, eds. ASM, Washington, DC, pp. 12–19.Google Scholar
  22. 22.
    Onyekaba, C. O., J. T. Harty, and P. G. W. Plagemann (1989) Extensive cytocidal replication of lactate dehydrogenase-elevating virus in cultured peritoneal macrophages from 1-and 2-week-old mice. Virus Res. 14, 327–338.PubMedGoogle Scholar
  23. 23.
    Stueckemann, J. A., D. Ritzi, M. Holth, M. Smith, W. J. Swart, W. A. Cafruny, and P. G. W. Plagemann (1982a) Replication of lactate dehydrogenase-elevating virus in macrophages. 1. Evidence for cyctocidal replication. J. Gen. Virol. 59, 245–262.PubMedGoogle Scholar
  24. 24.
    Stueckemann, J. A., M. Holth, W. J. Swart, K. Kowalchyk, M. S. Smith, A. J. Wolstenholm, W. A. Cafruny, and P. G. W. Plagemann (1982b) Replication of lactate dehydrogenase-elevating virus in macrophages. 2. Mechanism of persistent infection in mice and cell culture. J. Gen. Virol. 59, 263–272.PubMedGoogle Scholar
  25. 25.
    Tong, S. L., J. A. Stueckemann, and P. G. W. Plagemann (1977) Autoradiographic method for detection of lactate dehydrogenase-elevating virus-infected cells in primary mouse macrophage cultures. J. Virol. 22, 219–227.PubMedGoogle Scholar
  26. 26.
    Kowalchyk, K. and P. G. W. Plagemann (1985) Cell surface receptors for lactate dehyrogenase-elevating virus on subpopulation of macrophages. Virus Res. 2, 211–229.PubMedGoogle Scholar
  27. 27.
    Inada, T. and C. A. Mims (1985a) Pattern of infection and selective loss of la positive cells in suckling and adult mice inoculated with lactic dehydrogenase virus. Arch. Virol. 86, 151–165.PubMedGoogle Scholar
  28. 28.
    Plagemann, P. G. W., K. F. Gregory, H. E. Swim, and K. K. W. Chan (1963) Plasma lactate dehydrogenase-elevating agent of mice: Distribution in tissues and effects on lactate dehydrogenase isozyme patterns. Can. J. Microbiol. 9, 75–86.Google Scholar
  29. 29.
    Buxton, I. K., S. P. K. Chan, and P. G. W. Plagemann (1988) The I-A antigen is not the major receptor for lactate dehydrogenase-elevating virus on macrophages of CBA and BALB/c mice. Virus Res. 9, 205–219.PubMedGoogle Scholar
  30. 30.
    Inada, T. and C. A. Mims (1984) Mouse la antigens are receptors for lactate dehydrogenase virus. Nature, 309, 59–61.PubMedGoogle Scholar
  31. 31.
    Inada, T. and C. A. Mims (1985b) la antigens and Fc receptors of mouse peritoneal macrophages as determinants of susceptibility to lactic dehydrognease virus. J. Gen. Virol. 66, 1469–1477.PubMedGoogle Scholar
  32. 32.
    Inada, T. and C. A. Mims (1987) Genetic basis for la possitivity and susceptibility to lactic dehydrogenase virus in macrophages of SJL/J mice. Arch. Virol. 92, 77–86.PubMedGoogle Scholar
  33. 33.
    Onyekaba, C. O., J. T. Harty, C. Even, B. Hu, and P. G. W. Plagemann (1989) Persistent infection of mice by lactate dehydrogenase elevating virus: Effects of immunosuppression on virus replication and antiviral immune responses. Virus Res. 14, 297–316.PubMedGoogle Scholar
  34. 34.
    Chan, S. P. K., C. O. Onyekaba, J. T. Harty, and P. G. W. Plagemann (1989) Persistent infection of mice by lactate dehydrogenase-elevating virus: Transient virus replication in macrophages of the spleen. Virus Res. 14, 317–326.PubMedGoogle Scholar
  35. 35.
    Porter, D. D., G. H. Porter, and B. B. Deerhake (1969) Immunofluorescence assay for antigen and antibody in lactate dehydrogenase-virus infection in mice. J. Immunol. 102, 431–436.PubMedGoogle Scholar
  36. 36.
    Oldstone, M. B. A. (1989) Viral persistence. Cell 56, 517–520.PubMedGoogle Scholar
  37. 37.
    Coutelier, J. P., E. van Roost, P. Lambotte, and J. Van Snick (1986) The murine antibody response to lactate dehydrogenase-elevating virus. J. Gen. Virol. 67, 1099–1108.PubMedGoogle Scholar
  38. 38.
    Cafruny, W. A. and P. G. W. Plagemann (1982) Immune response to lactate dehydrogenase-elevating virus: Serologically specific rabbit neutralizing antibody to the virus. Infect. Immun. 37, 1001–1006.PubMedGoogle Scholar
  39. 39.
    McDonald, T. L. (1982) Isolation of C1q-binding virus-antibody immune complexes from lactate dehydrogenase-elevating virus (LDV)-infected mice. Immunology 45, 365–370.PubMedGoogle Scholar
  40. 40.
    McDonald, T. L., T. Donnelly, A. Weber, and L. Quenette (1983) Antibody classes and subclasses in circulating immune complexes isolated from mice infected with lactate dehydrogenase-elevating virus. Immunology 48, 511–517.PubMedGoogle Scholar
  41. 41.
    Notkins, A. L., S. Mahar, C. Scheele, and J. Goffman (1966) Infectious virus-antibody complexes in the blood of chronically infected mice. J. Exp. Med. 124, 81–97.PubMedGoogle Scholar
  42. 42.
    Harty, J. T. and P. G. W. Plagemann (1988) Formalin inactivation of the lactate dehydrogenase-elevating virus reveals a major neutralizing epitope not recognized during natural infection. J. Virol. 62, 3210–3216.PubMedGoogle Scholar
  43. 43.
    Notkins, A. L., M. Mage, W. K. Ashe, and S. Mahar (1968) Neutralization of sensitized lactic dehydrogenase virus by anti-γ globulin. J. Immunol. 100, 314–320.PubMedGoogle Scholar
  44. 44.
    Smit, J. J., A. M. Duursma, J. M. W. Bouma, and M. Gruber (1987) Receptor-mediated endocytosis of lactate dehydrogenase M4 by liver macrophages: A mechanism for elimination of enzymes from plasma. Evidence for competition by creatine kinase MM, adenylate kinase, malate and alcohol dehydrogenase. J. Biol. Chem. 262, 13020–13026.PubMedGoogle Scholar
  45. 45.
    Michaelides, M. C. and E. S. Simms (1980) Immune response in mice infected with lactate dehydrogenase virus. III Antibody response to a T-dependent and a T-independent antigen during acute and chronic LDV infection. Cell. Immunol. 50, 253–260.PubMedGoogle Scholar
  46. 46.
    Notkins, A. L., S. E. Mergenhagen, A. A. Rizzo, C. Scheele, and T. A. Waldman (1966) Elevated γ globulin and increased antibody production in mice infected with lactic dehydrogenase virus. J. Exp. Med. 123, 347–364.PubMedGoogle Scholar
  47. 47.
    Coutelier, J. P. and J. Van Snick (1985) Isotypically restricted activation of B lymphocytes by lactic dehydrogenase virus. Eur. J. Immunol. 15, 250–255.PubMedGoogle Scholar
  48. 48.
    Coutelier, J. P., P. G. Coulie, P. Wauters, H. Heremans, and J. T. M. van der Logt (1990) In vivo polyclonal B-lymphocyte activation elicited by murine viruses. J. Virol. 64, 5383–5388.PubMedGoogle Scholar
  49. 49.
    Harty, J. T., S. P. K. Chan, and P. G. W. Plagemann (1987) Charateristics of monoclonal antibodies to the lactate dehydrogenase-elevating virus. Intervirology 27, 53–60.PubMedGoogle Scholar
  50. 50.
    U X., B. Hu, J. Harty, C. Even, and P. G. W. Plagemann (1990) Polyclonal activation of IgG2a and IgG2b production by infection of mice with lactate dehydrogenase-elevating virus is partly dependent on CD4+ lymphocytes. Viral Immunol. 3(4), 273–288.Google Scholar
  51. 51.
    Cafruny, W. A. and D. Hovinen. (1988) Infection of mice with lactate dehydrogenase-elevating virus leads to stimulation of autoantibodies. J. Gen. Virol. 69, 723–729.PubMedGoogle Scholar
  52. 52.
    Weiland, E., F. Weiland, and A. Grossmann (1987) Lactate dehydrogenase-elevating virus induces anti-Golgi apparatus antibodies. J. Gen. Virol. 68, 1983–1991.PubMedGoogle Scholar
  53. 53.
    Weiland, E., A. Grossmann, H.-J. Thiel, and F. Weiland (1990) Lactate dehydrogenase-elevating virus induces antibodies reactive with a surface antigen of aetiologically unrelated in murine cell transformants. J. Gen. Virol. 71, 1233–1236.PubMedGoogle Scholar
  54. 54.
    Murphy, W. H., J. R Nawrocki, and L. R. Pease (1980) Aetiological mechanisms in age-dependent murine motor neuron disease, in Animal Models of Neurological Disease P. O. Behan and R C. Rose, eds. Pitman Medical, Turnbridge Wells, UK, pp. 123–135.Google Scholar
  55. 55.
    Pease, L. R., G. D. Abrams, and W. H. Murphy (1982) Fv-1 restriction of age-dependent paralytic lactate dehydrogenase-elevating virus infection. Virology 117, 29–37.PubMedGoogle Scholar
  56. 56.
    Contag, C. H. and P. G. W. Plagemann (1989) Age-dependent poliomyelitis of mice: Expression of an endogenous retrovirus correlates with cytocidal replication of lactate dehydrogenase-elevating virus in motor neurons. J. Virol. 63, 4362–4369.PubMedGoogle Scholar
  57. 57.
    Stroop, W. G., J. Weibel, D. Schaeffer, and M. A. Brinton (1983) Mouse strain-specific central nervous system lesions associated with lactate dehyrogenase-elevating virus infection. Lab. Invest. 49, 334–344.PubMedGoogle Scholar
  58. 58.
    Brinton, M. A., E. I. Gavin, and J. Weibel (1986) Detection of viral-specific nucleic acid and intracellular virions in ventral horn neurons of lactate dehydrogenase-elevating virus infected C58 mice. Microb. Pathogen. 1, 595–602.Google Scholar
  59. 59.
    Contag, C. H., S. P. K. Chan, S. W. Wietgrefe, and P. G. W. Plagemann (1986) Correlation between presence of lactate dehydrogenase-elevating virus RNA and antigens in motor neurons and paralysis in infected C58 mice. Virus Res. 6, 195–209.PubMedGoogle Scholar
  60. 60.
    Contag, C. H. and P. G. W. Plagemann (1988) Susceptibility of C58 mice to paralytic disease induced by lactate dehydrogenase-elevating virus correlates with increased expression of endogenous retroviruses in motor neurons. Microb. Pathogen. 5, 287–296.Google Scholar
  61. 61.
    Stroop, W. G. and M. A. Brinton (1985) Ultrastructural and immunofluorescence studies of acute and chronic lactate dehydrogenase-elevating virus-induced nonparalytic poliomyelitis in mice. Proc. Soc. Exp. Biol. Med. 178, 261–274.PubMedGoogle Scholar
  62. 62.
    Andrews, J. M. and M. B. Gardner (1974) Lower motor neuron degeneration associated with type C RNA virus infection in mice: Neuropathological features. J. Neuropathol. Exp. Neurol. 33, 285–307.PubMedGoogle Scholar
  63. 63.
    Gardner, M. B. (1989) in Neuroimmune Networks: Physiology and Disease. E. J. Goetzel and N. H. Spector, eds. Alan R. Liss, New York, pp. 179–192.Google Scholar
  64. 64.
    Beck, E., D. M. Daniel, A. J. Davey, D. C. Gajdusek, and C. J. Gibbs (1982) The pathogenesis of transmissible spongiform encephalopathy. An ultrastructural study. Brain 105, 755–786.PubMedGoogle Scholar
  65. 65.
    Fishman, H. M., K. P. Tewari, and P. G. Stein (1990) Injury-induced vasiculation and membrane redistribution in squid giant axon. Biochem. Biophys. Acta 1023, 421–425.PubMedGoogle Scholar
  66. 66.
    Chalfie, M. and E. Wolinsky (1990) The identification and suppression of inherited neurodegeneration in Caenorhabditis elegans. Nature 345, 410–416.PubMedGoogle Scholar
  67. 67.
    Gajdusek, D. C. (1977) Unconventional viruses and the disappearance of Kuru. Science 197, 943–959.PubMedGoogle Scholar
  68. 68.
    Cafruny, W. A., C. R. Strancke, K. Kowalchyk, and P. G. W. Plagemann (1986) Replication of lactate dehydrogenase-elevating virus in C58 mice and quantitiation of anti-viral antibodies and of tissue virus levels as a function of development of paralytic disease. J. Gen. Virol. 67, 27–37.PubMedGoogle Scholar
  69. 69.
    Kascsak, R. J., R. I. Carp, H. Donnenfeld, and H. Bartfeld (1983) Kinetics of replication of lactate dehydrogenase-elevating virus in age-dependent polioencephalomyelitis. Intervirology 19, 6–15.PubMedGoogle Scholar
  70. 70.
    Harty, J. T. and P. G. W. Plagemann (1990) Monoclonal antibody protection from age-dependent poliomyelitis: Implications regarding the pathogenesis of lactate dehydrogenase-elevating virus. J. Virol. 64, 6257–6262.PubMedGoogle Scholar
  71. 71.
    Peluso, R., A. T. Haase, L. Stowring, M. Edwards, and P. Ventura (1985) A Trojan horse mechanism for the spread of visna virus in monocytes. Virology 147, 231–236.PubMedGoogle Scholar
  72. 72.
    Johnson, R. T. (1982) Virus infections of the nervous system. Raven, New York, pp 36–60.Google Scholar
  73. 73.
    Tyler, K. L., D. A. McPhee, and B. N. Fields (1986) Distinct pathways of viral spread in the host determined by reovirus S1 segment. Science 233, 770–774.PubMedGoogle Scholar
  74. 74.
    Johnson, R. T., J. C. McArthur, and O. Narayan (1988) The neurobiology of human immunodeficiency virus infections. FASEB J. 2, 2970–2981.PubMedGoogle Scholar
  75. 75.
    Coffin, J. M. (1985) Endogenous retroviruses, in RNA Tumor Viruses, vol. 2. R. Weiss, N. Teich, H. Varmus, and J. M Coffin, eds. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 1109–1203.Google Scholar
  76. 76.
    Jenkins, N., N. G. Copeland, B. A. Taylor, and B. K. Lee (1982) Organization, distribution and stability of endogenous ecotropic murine leukemia virus DNA sequences in chromosomes of Mus musculus. J. Virol. 42, 26–36.Google Scholar
  77. 77.
    Kozak, C. (1985) Retroviruses as chromosomal genes in the mouse. Adv. Cancer Res. 44, 295–336.PubMedGoogle Scholar
  78. 78.
    Coffin, J. M. (1990) Retroviridae and their replication, in Virology. B. M. Fields and D. M. Knipe, eds. vol 2. Raven, New York, pp. 1437–1500.Google Scholar
  79. 79.
    Stoye, J. P. and J. M. Coffin (1987) The four classes of endogenous murine leukemia virus: Structural relationships and potential for recombination. J. Virol. 61, 2659–2669.PubMedGoogle Scholar
  80. 80.
    Stoye, J. P. and J. M. Coffin (1988) Polymorphism of murine endogenous proviruses revealed by using virus class-specific oligonucleotide probes. J. Virol. 62, 168–175.PubMedGoogle Scholar
  81. 81.
    Varmus, H. and P. Brown (1989) Retrovirus, in Mobile DNA. D. E. Berg and M. M. Howe, eds. AMS, Washington, D. C, pp. 53–108.Google Scholar
  82. 82.
    Lowy, D. R., E. Rands, S. K. Chattopadhyay, C. F. Garon, and G. L. Hager (1980) Molecular cloning of infectious, integrated murine leukemia virus DNA from infected mouse cells. Proc. Natl. Acad. Sci. USA 77, 614–618.PubMedGoogle Scholar
  83. 83.
    Boone, L. R., P. L. Glover, C. L. Innes, L. A. Niver, M. C. Bondurant, and W. K. Yang (1988) Fv-1 N-and B-tropism specific sequences in murine leukemia virus and related endogenous proviral genomes. J. Virol. 62, 2644–2650.PubMedGoogle Scholar
  84. 84.
    Des Groseillers, L. and P. Jolicoeur (1983) Physical mapping of the Fv-1 tropism host range determinant of BALB/c murine leukemia viruses. J. Virol. 48, 685–696.Google Scholar
  85. 85.
    Jolicouer, P. (1979) The Fv-1 gene of the mouse and its control of murine leukemia virus replication. Curr. Top. Microbiol. Immunol. 86, 67–122.Google Scholar
  86. 86.
    O’Brien, S. J., E. J. Berman, J. D. Estes, and M. B. Gardner (1983) Murine retroviral restriction genes Fv-4 and Akv-1 are alleles of a single locus. J. Virol. 47, 649–651.Google Scholar
  87. 87.
    Lowy, D. R., S. K. Chattopadhyay, N. M. Teich, W. P. Rowe, and A. S. Levine (1974) AKR murine leukemia virus genome. Frequencies in DNA of high and non-virus-yielding mouse strains. Proc. Natl. Acad. Sci. USA 71, 3555–3559.PubMedGoogle Scholar
  88. 88.
    Laigret, T., R. Repaske, V. Boulukus, A. B. Rabson, and A. S. Kahn (1988) Potential progenitor sequences of mink cell focus forming (MCF) murine leukemia viruses: Ecotropic, xenotropic and MCF-related viral RNAs are detected concurrently in thymus tissues of AKR mice. J. Virol. 62, 376–386.PubMedGoogle Scholar
  89. 89.
    Varmus, H. (1988) Retroviruses. Science 240, 1427–1434.PubMedGoogle Scholar
  90. 90.
    Harty, J. T., S. P. K. Chan, C. H. Contag, and P. G. W. Plagemann (1987) Protection of C58 mice from lactate dehydrogenase-elevating virus-induced motor neuron disease by non-neutralizing antiviral antibodies without interference with virus replication. J. Neuroimmunol. 15, 195–206.PubMedGoogle Scholar
  91. 91.
    Bently, D. M. and R. E. Morris (1982) T cell subsets required for protection against age-dependent polioencephalomyelitis of C58 mice. J. Immunol. 128, 530–534.Google Scholar
  92. 92.
    Bently, D. M., S. R. Watson, and R. E. Morris (1983) Age-related loss of Lyt 1, 2 cells in C58 mice results in susceptibility to lactate dehydrogenase virus-induced polioencephalomyelitis. Infect. Immun. 41, 1389, 1390.Google Scholar
  93. 93.
    Martinez, D., M. Brinton, T. G. Tachovsky, and A. H. Phelps (1980) Identification of lactate dehydrogenase-elevating virus as the etiological agent of genetically restricted, age-dependent polioencephalomyelitis of mice. Infect. Immun. 27, 979–987.PubMedGoogle Scholar
  94. 94.
    Brinton, M. A., E. I. Gavin, and A. V. Fernandez (1986) Geotypic variation among six isolates of lactate dehydrognease-elevating virus. J. Gen. Virol. 67, 2673–2684.PubMedGoogle Scholar
  95. 95.
    Contag, C. H., E. F. Retzel, and P. G. W. Plagemann (1986) Genomic differences between strains of lactate dehydrogenase-elevating virus. Intervirology 26, 228–233.PubMedGoogle Scholar
  96. 96.
    Duffy, P. S., D. Martinez, G. D. Abrams, and W. H. Murphy (1976) Pathogenic mechanisms in immune polioencephalomyelitis: Induction of disease in immunosuppressed mice. J. Immunol. 116, 475–481.Google Scholar
  97. 97.
    Whitton, J. L. and M. B. A. Oldstone (1990) Virus-induced immune response interactions. Principles of immunity and immunopathology, in Virology. B. M. Fields and D. M. Knipe eds. vol. 1, Raven, New York, pp. 369–381.Google Scholar
  98. 98.
    Oldstone, M. B. A., P. Blount, P. J. Southern, and P. W. Lampert (1986) Cytoimmunotherapy for persistent virus infection reveals a unique clearance pattern from the central nervous system. Nature 321, 239–243.PubMedGoogle Scholar
  99. 99.
    Klavinskis, L. S., R. Geckeler, and M. B. A. Oldstone (1989) Cytototic T lymphocytes control of acute lymphocytic choriomeningitis virus infection: Interferon gamma, but not tumor necrosis factor a, displays antiviral activity in vivo. J. Gen. Virol. 70, 3317–3325.PubMedGoogle Scholar
  100. 100.
    Brody, J. A. and C. J. Gibbs (1984) Chronic neurological diseases, in Viral Infections of Humans: Epidemiology, 2nd Ed. A. S. Evans, ed. Plenum, New York.Google Scholar
  101. 101.
    Mulder, D. W. (1982) Clinical limits of amyotropic lateral selerosis. Adv. Neurol. 36, 15–29.PubMedGoogle Scholar
  102. 102.
    Heston, L. L. (1985) Genetic relationships in early onset Alzeimer’s disease and Downs syndrome. New insights. Ann. Intern. Med. 103, 566–578.PubMedGoogle Scholar
  103. 103.
    Mager, D. L. and J. D. Freeman (1987) Human endogenous retrovirus-like genome with type C pol sequences and gag sequences related to human T-cell lymphotropic viruses. J. Virol. 61, 4060–4066.PubMedGoogle Scholar
  104. 104.
    Mariani-Costantini, R., T. M. Horn, and R. Callahan (1989) Ancestry of a human endogenous retrovirus family. J. Virol. 63, 4982–4985.PubMedGoogle Scholar
  105. 105.
    Kato, N., S. Pfeiffer-Ohlsson, M. Kato, E. Larrson, J. Rydnert, R. Ohlsson, and M. Cohen (1987) Tissue-specific expression of human provirus ERV3 mRNA in human placenta: Two of three ERV3 mRNAs contain human cellular sequences. J. Virol. 61, 2182–2191.PubMedGoogle Scholar
  106. 107.
    Copeland, N. G., N. A. Jenkins, B. Nexo, A. M. Schultz, A. Rein, T. Mikkelsen, and P. Jorgensen (1988) Poorly expressed endogenous eco-tropic provirus of DBA/2 mice encodes a mutant Pr65gag protein that is not myristylated. J. Virol. 62, 479–87.PubMedGoogle Scholar
  107. 108.
    Mercer, J. A., N. A. Jenkins, and N. G. Copeland (1990) Lack of ecotropic virus involvement in induction of lymphomas in DBA/2J mice by 7, 12-dimethylbenz(a)anthracene. J. Virol. 64, 5199–5203.PubMedGoogle Scholar
  108. 109.
    Jenkins N. A., N. G. Copeland, B. A. Taylor, and B. K. Lee (1981) Dilute (d) coat colour mutation of DBA/2J mice is associated with the site of integration of an ecotropic MuLV genome. Nature 293, 370–374.PubMedGoogle Scholar
  109. 110.
    Bothe, K., A. Aguzzi, H. Lassmann, A. Rethwilm, and I. Horak (1991) Progressive encephalopathy and myopathy in transgenic mice expressing human foamy virus genes. Science 253, 555–557.PubMedGoogle Scholar
  110. 111.
    Sharpe A. H., J. J. Hunter, P. Chassler, and R. Jaenisch (1991) Role of abortive retroviral infection of neurons in spongiform CNS degeneration. Nature 346, 181–183.Google Scholar
  111. 112.
    Kay, D. G., C. Gravel, Y. Robitaille, and P. Jolicoeur (1991) Retrovirus-induced spongiform myeloencephalopathy in mice: Regional distribution of infected target cells and neuronal loss occurring in the absence of viral expression in neurons. Proc. Natl. Acad. Sci. USA 88, 1281–1285.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Christopher H. Contag
  • John T. Harty
  • Peter G. W. Plagemann

There are no affiliations available

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