Pathogenesis of Intrauterine Infections of the Brain

  • Jerome E. Kurent
  • John L. Sever


Among the most devastating consequences of intrauterine infection for the developing fetus are those that involve the central nervous system (CNS). These infections may produce severe neurological disease and death. In addition, although the great majority of human CNS anomalies are without recognized etiology or are simply attributed to “defects of embryogenesis,” there is a growing appreciation that microorganisms, and particularly viruses, have the potential of producing these defects as sequelae to intrauterine infections. This has stimulated efforts to understand their pathogenesis and to discover additional virus-host relationships existing within this significant group of diseases.


Newcastle Disease Virus Cerebellar Ataxia Rubella Virus Maternal Infection Aqueductal Stenosis 
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.


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  1. 1.
    C. A. Mims, Pathogenesis of viral infections of the fetus, Prog. Med. Virol. 10:194–237 (1968).Google Scholar
  2. 2.
    L. W. Catalano and J. L. Sever, The role of viruses as causes of congenital defects, Ann. Rev. Microbiol. 25:255–282 (1971).CrossRefGoogle Scholar
  3. 3.
    E. Traub, The epidemiology of lymphocytic choriomeningitis in white mice, J. Exp. Med. 64:183–200 (1936).CrossRefGoogle Scholar
  4. 4.
    J. E. Hotchin and M. Cinits, Lymphocytic choriomeningitis infection of mice as a model for the study of latent virus infection, Can. J. Microbiol. 4:149–163 (1958).CrossRefGoogle Scholar
  5. 5.
    C. Mims, Immunofluorescence study of the carrier state and mechanism of vertical transmission in lymphocytic choriomeningitis viral infection in mice, J. Pathol. Bacteriol. 91:395–402 (1966).CrossRefGoogle Scholar
  6. 6.
    D. J. Lang and J. F. Kummer, Demonstration of cytomegalovirus in semen, N. Engl. J. Med. 287:756–758 (1972).CrossRefGoogle Scholar
  7. 7.
    A. Dekaban, J. O’Rourke, and T. Corman, Abnormalities in offspring related to maternal rubella during pregnancy, Neurology 8:387–392 (1958).CrossRefGoogle Scholar
  8. 8.
    R. H. Michaels and G. W. Mellin, Prospective experience with maternal rubella and the associated congenital malformations, Pediatrics 26:200–209 (1960).Google Scholar
  9. 9.
    R. Lundstrom, Rubella during pregnancy, Acta Paediatr. Scand. 51, Suppl. 133:1–110 (1962).Google Scholar
  10. 10.
    B. I. Osburn, A. M. Silverstein, R. A. Prendergast, R. T. Johnson, and C. J. Parshall, Experimental viral-induced congenital encephalopathies. I. Pathology of hydranencephaly and porencephaly caused by bluetongue vaccine virus, Lab. Invest. 25:197–205 (1971).Google Scholar
  11. 11.
    N. Gregg, Congenital cataract following German measles in the mother, Trans. Opthalmol. Soc.Aust. 3:35–46 (1941).Google Scholar
  12. 12.
    S. B. Korones, L. E. Ainger, G. R. G. Monif, J. Roane, J. L. Sever, and R. Fuste, Congenital rubella syndrome: New clinical aspects with recovery of virus from affected infants, J. Pediatr. 67:166–181 (1965).CrossRefGoogle Scholar
  13. 13.
    I. Jack and J. Grutzner, Cellular viraemia in babies infected with rubella virus before birth, Br. Med. J. 1:289–292 (1969).CrossRefGoogle Scholar
  14. 14.
    M. A. Menser, J. D. Harley, R. Hertzberg, O. C. Dorman, and A. C. Murphy, Persistence of virus infections for three years after prenatal rubella, Lancet 2:387–388 (1967).CrossRefGoogle Scholar
  15. 15.
    R. L. Naeye and W. Blanc, Pathogenesis of congenital rubella, J. Am. Med. Assoc. 194:1277–1283 (1965).CrossRefGoogle Scholar
  16. 16.
    W. E. Rawls and J. L. Melnick, Rubella virus carrier cultures derived from congenitally infected infants, J. Exp. Med. 123:795–816 (1966).CrossRefGoogle Scholar
  17. 17.
    S. A. Plotkin, A. Boue, and J. G. Boue, The in vitro growth of rubella virus in human embryo cells, Am. J. Epidemiol. 81:71–85 (1965).Google Scholar
  18. 18.
    S. A. Plotkin and A. Vaheri, Human fibroblasts infected with rubella virus produce a growth inhibitor, Science (Wash. D.C.) 156:659–661 (1967).CrossRefGoogle Scholar
  19. 19.
    P. B. Dent and A. E. Rawls, Human congenital rubella: The relationship of immunologic aberration to viral persistence, Ann. N.Y. Acad. Sci. 181:209–222 (1971).CrossRefGoogle Scholar
  20. 20.
    J. F. K. Soothill, J. A. Hayes, and J. A. Dugeon, Immunoglobulin in congenital rubella, Lancet 1:1385–1388 (1966).CrossRefGoogle Scholar
  21. 21.
    M. P. Hancock, C. C. Huntley, and J. L. Sever, Congenital rubella syndrome with Immunoglobulin disease, J. Pediatr. 72:636–645 (1968).CrossRefGoogle Scholar
  22. 22.
    R. N. Schimke, C. Bolano, and C. H. Kirkpatrick, Immunologie deficiency in the congenital rubella syndrome, Am. J. Dis. Child. 118:626–633 (1969).Google Scholar
  23. 23.
    T. C. Doege and K. S. W. Kim, Studies of rubella and its prevention with immune globulin, J. Am. Med. Assoc. 200:584–590 (1967).CrossRefGoogle Scholar
  24. 24.
    M. A. Menser, L. Dods, and J. D. Harley, A twenty-five year followup of congenital rubella, Lancet 2:1347–1350 (1967).CrossRefGoogle Scholar
  25. 25.
    K. E. Kenrick, R. F. Slinn, D. C. Dorman, and M. A. Menser, Immunoglobulin and rubellavirus antibodies in adults with congenital rubella, Lancet 1:548–551 (1968).CrossRefGoogle Scholar
  26. 26.
    J. B. Hardy, J. L. Sever, and M. R. Gilkeson, Declining antibody titers in children with congenital rubella, J. Pediatr. 75:213–220 (1969).CrossRefGoogle Scholar
  27. 27.
    A. L. Florman, L. Z. Cooper, P. R. Ziring, and S. Krugman, Response to rubella vaccine among seronegative children with congenital rubella, Pediatr. Res. 4:372–373 (1970).CrossRefGoogle Scholar
  28. 28.
    J. R. Montgomery, M. A. South, W. E. Rawls, J. L. Melnick, G. B. Olson, P. B. Dent, and R. A. Good, Viral inhibition of lymphocyte response to phytohemagglutinin, Science (Wash. D.C.) 157:1068–1070 (1967).CrossRefGoogle Scholar
  29. 29.
    G. B. Olson, M. A. South, and R. A. Good, Phytohemagglutinin unresponsiveness of lymphocytes from babies with congenital rubella, Nature (Lond.) 214:695–696 (1967).CrossRefGoogle Scholar
  30. 30.
    J. W. Uhr and G. Muller, Regulatory effect of antibody on the immune response, Adv. Immunol. 81:81–127 (1968).CrossRefGoogle Scholar
  31. 31.
    D. N. Medearis, Cytomegalic inclusion disease — An analysis of the clinical features based on the literature and six additional cases, Pediatrics 19:467–480 (1957).Google Scholar
  32. 32.
    J. B. Hanshaw, Congenital and acquired cytomegalovirus infection, Pediatr. Clin. N. Am. 13:279–293 (1966).Google Scholar
  33. 33.
    J. L. Sever and L. R. White, Intrauterine viral infections, Ann. Rev. Med. 19:471–486 (1968).CrossRefGoogle Scholar
  34. 34.
    R. J. Hildebrandt, J. L. Sever, A. M. Margileth, and C. A. Callagan, Cytomegalovirus in the normal pregnant woman, Am. J. Obstet. Gynecol. 98:1125–1128 (1967).Google Scholar
  35. 35.
    R. A. Feldman, Cytomegalovirus infection during pregnancy, Amer. J. Dis. Child. 117:517–521 (1969).Google Scholar
  36. 36.
    G. Birnbaum, J. I. Lynch, A. M. Margileth, W. M. Lonergan, and J. L. Sever, Cytomegalovirus infection in newborn infants, J. Pediatr. 75:789–795 (1969).CrossRefGoogle Scholar
  37. 37.
    D. J. Lang and D. Noren, Cytomegaloviremia following congenital infection. Pediatr. 37:812–819 (1968).Google Scholar
  38. 38.
    C. A. Alford, J. W. Foft, W. J. Blankenship, G. Cassady, and J. W. Benton, Subclinical central nervous system disease of neonates: A prospective study of infants born with increased levels of IgM, J. Pediatr. 75:1167–1178 (1962).CrossRefGoogle Scholar
  39. 39.
    J. B. Hanshaw, Cytomegalovirus complement-fixing antibody in microcephaly, New Engl. J. Med. 275:476–479 (1966).CrossRefGoogle Scholar
  40. 40.
    S. Kibrick and G. W. Gooding, Pathogenesis of infection with herpes simplex virus with special reference to nervous tissue, in “Slow, Latent and Temperate Virus Infections” (D. C. Gajdusek, C. J. Gibbs, Jr., and M. Alpers, eds.) pp. 143–154, U.S. Government Printing Office, Washington (1965).Google Scholar
  41. 41.
    A. J. Nahmias and W. R. Dowdle, Antigenic and biologic difference in herpesvirus hominis, Prog. Med. Virol. 10:110–159(1968).Google Scholar
  42. 42.
    M. A. South, W. A. F. Tompkins, C. R. Morris, and W. E. Rawls, Congenital malformation of the central nervous system associated with genital type (type 2) herpesvirus, J. Pediatr. 75:13–18, (1969).CrossRefGoogle Scholar
  43. 43.
    A. L. Florman, A. A. Gershon, P. R. Blackett, and A. J. Nahmias, Intrauterine infection with herpes simplex virus: Resultant congenital malformations, J. Am. Med. Assoc. 225:129–132 (1973).CrossRefGoogle Scholar
  44. 44.
    A. J. Nahmias, W. R. Dowdle, W. E. Josey, Z. M. Naib, C. M. Painter, and C. Luce, Newborn infections with herpesvirus homonis types 1 and 2, J. Pediatr. 75:1194–1203 (1969).CrossRefGoogle Scholar
  45. 45.
    R. T. Johnson, The pathogenesis of herpesvirus encephalitis. I. Virus pathways to the nervous system of suckling mice demonstrated by fluorescent antibody staining, J. Exp. Med. 119:343–356 (1964).CrossRefGoogle Scholar
  46. 46.
    E. W. Goodpasture and O. Teague, Transmission of the virus of herpes febrilis along nerves in experimentally infected rabbits, J. Med. Res. 44:139–184 (1923).Google Scholar
  47. 47.
    C. R. Boughton, Toxoplasmosis, Med. J. Aust. 2:418–421 (1970).Google Scholar
  48. 48.
    J. K. A. Beverley, Toxoplasmosis, Br. Med. J. 2:475–478 (1973).CrossRefGoogle Scholar
  49. 49.
    W. M. Hutchison, J. F. Dunachie, J. C. Sum, and K. Work, Coccidian-like nature of Toxoplasma gondii, Br. Med. J. 1:142–144 (1970).CrossRefGoogle Scholar
  50. 50.
    J. K. Frenkel, J. B. Dubey, and N. L. Miller, Toxoplasma gondii: The oocyst, sporozoite, and infection of cultured cells, Science (Wash. D.C.) 167:892–896 (1970).CrossRefGoogle Scholar
  51. 51.
    O. S. Hume, Toxoplasmosis and pregnancy, Am. J. Obstet. Gynecol. 114:703–715 (1972).Google Scholar
  52. 52.
    H. F. Eichenwald, A study of congenital toxoplasmosis with particular emphasis on clinical manifestations, sequelae and therapy, in “Human Toxoplasmosis” (J. C. Siim, ed.) pp. 41–49, Williams & Wilkins, Baltimore (1960).Google Scholar
  53. 53.
    G. Altschuler, Toxoplasmosis as a cause of hydranencephaly, Am. J. Dis. Child. 125:251–252 (1973).Google Scholar
  54. 54.
    J. A. Prior, C. R. Cole, F. L. Doctor, S. Saslaw, and D. M. Chamberlain, Toxoplasmosis. IV. Report of three cases with particular reference to asymptomatic parasitemia in a young woman, Arch. Intern. Med. 92:314–320 (1953).CrossRefGoogle Scholar
  55. 55.
    M. J. Miller, W. J. Aronson, and J. S. Remington, Late parasitemia in asymptomatic acquired toxoplasmosis, Ann. Intern. Med. 71:139–145 (1969).Google Scholar
  56. 56.
    V. L. Sanger and C. R. Cole, Toxoplasmosis. VI. Isolation of toxoplasma from milk, placentas, and newborn pigs of asymptomatic carrier sows, Am. J. Vet. Res. 16:536–539 (1955).Google Scholar
  57. 57.
    J. K. A. Beverley, Congenital transmission of toxoplasmosis through successive generations of mice, Nature (Lond.) 183:1348–1349 (1959).CrossRefGoogle Scholar
  58. 58.
    J. S. Remington, L. Jacobs, and M. L. Melton, Congenital transmission of toxoplasmosis from mother, J. Infect. Dis. 108:163–173 (1961).CrossRefGoogle Scholar
  59. 59.
    H. Eichenwald, Experimental toxoplasmosis, Am. J. Dis. Child. 76:307–315 (1948).Google Scholar
  60. 60.
    H. Eichenwald, Experimental toxoplasmosis. II. Effect of sulfadiazine and antiserum on congenital toxoplasmosis in mice, Proc. Soc. Exp. Biol. Med. 71:45–49 (1949).Google Scholar
  61. 61.
    W. R. Holder and J. M. Knox, Syphilis in pregnancy, Med. Clin. N. Am. 56:1151–1160 (1972).Google Scholar
  62. 62.
    A. J. Steigman, Spirochetal infections, in “Textbook of Pediatrics” (W. E. Nelson, V. C. Vaughan, and R. J. McKay, eds.) pp. 614–623, Saunders, Philadelphia (1969).Google Scholar
  63. 63.
    A. M. Silverstein, Congenital syphilis and the timing of immunogenesis in the human fetus, Nature (Lond.) 194:196–197 (1962).CrossRefGoogle Scholar
  64. 64.
    A. M. Silverstein, Ontogeny of the immune response, Science (Wash. D.C.) 144:1423–1428 (1964).CrossRefGoogle Scholar
  65. 65.
    R. T. Johnson, Effects of viral infections on the developing nervous system, N. Engl. J. Med. 287:599–604 (1972).CrossRefGoogle Scholar
  66. 66.
    V. Hamburger K. Habel, Teratogenic and lethal effects of influenza A and mumps viruses on early chick embryos, Proc. Soc. Exp. Biol. Med. 66:608–617 (1947).Google Scholar
  67. 67.
    K. P. Johnson and R. Klasnja, Neural tube abnormalities produced in chick embryos with influenza A virus, J. Neuropath. Exp. Neurol. 29:133 (1970).CrossRefGoogle Scholar
  68. 68.
    G. G. Robertson, A. P. Williamson, and R. J. Blattner, A study of abnormalities in early chick embryos inoculated with Newcastle disease virus, J. Exp. Zool. 129:5–43 (1955).CrossRefGoogle Scholar
  69. 69.
    A. P. Williamson, R. J. Blattner, and G. G. Robertson, The relationship of viral antigen to virus-induced defects in chick embryos: Newcastle disease virus, Dev. Biol. 12:498–519 (1965).CrossRefGoogle Scholar
  70. 70.
    W. T. London, S. G. Kent, and J. L. Sever, Influenza virus — A teratogen in rhesus monkeys, presented at the Annual Meeting of the Federation of the American Society for Experimental Biology, Atlantic City, New Jersey, April 1973.Google Scholar
  71. 71.
    L. Kilham, G. Margolis, and E. D. Colby, Cerebellar ataxia and its congenital transmission in cats by feline panleukopenia virus, J. Am. Vet. Med. Assoc. 158:888–901 (1971).Google Scholar
  72. 72.
    L. Kilham, G. Margolis, and E. D. Colby, Congenital infections of cats and ferrets by feline panleukopenia virus manifested by cerebellar hypoplasia, Lab. Invest. 17:465–480 (1967).Google Scholar
  73. 73.
    G. Siegl, C. Hallauer, A. Novak, and G. Kronauer, Parvoviruses as contaminants of permanent human cell lines. II. Physicochemical properties of the isolated viruses, Arch. Gesamte Virusforsch. 35:91–103 (1971).CrossRefGoogle Scholar
  74. 74.
    L. Kilham and G. Margolis, Cerebellar ataxia in hamsters inoculated with rat virus, Science (Wash. D.C.) 143:1047–1048 (1964).CrossRefGoogle Scholar
  75. 74a.
    G. Margolis and L. Kilham, In pursuit of an ataxic hamster, or virus-induced cerebellar hypoplasia, in “The Central Nervous System,” International Academy of Pathology Monograph No. 9, pp 157–183, Williams & Wilkins, Baltimore (1968).Google Scholar
  76. 74b.
    G. Margolis and L. Kilham, Cerebellar ontogenetic patterns: Key to a virus code, in “The Cerebellum in Health and Disease” (W. S. Fields and W. D. Willis, Jr., eds.) pp 353–379, Warren H. Green, St. Louis (1970).Google Scholar
  77. 75.
    P. G. Howell and D. W. Verwood, Bluetongue virus, Virol. Monogr. 9:35–74 (1971).Google Scholar
  78. 76.
    G. Schultz and P. D. DeLong, Losses in newborn lambs associated with bluetongue vaccination of pregnant ewes, J. Am. Vet. Med. Assoc. 127:224–226 (1955).Google Scholar
  79. 77.
    S. Young and D. R. Cordy, An ovine fetal encephalopathy caused by bluetongue vaccine virus, J. Neuropathol. Exp. Neurol. 23:635–659 (1964).CrossRefGoogle Scholar
  80. 78.
    W. P. C. Richards and D. R. Cordy, Bluetongue virus infections pathologic responses of nervous systems in sheep and mice, Science (Wash. D.C.) 156:530–531 (1967).CrossRefGoogle Scholar
  81. 79.
    B. I. Osburn, R. T. Johnson, A. M. Silverstein, R. A. Prendergast, M. J. Jochim, and S. E. Levy, Experimental viral-induced congenital encephalopathies. II. The pathogenesis of bluetongue virus infection in fetal lambs, Lab. Invest. 25:206–210 (1971).Google Scholar
  82. 80.
    O. Narayan and R. T. Johnson, Effects of viral infection on nervous system development. I. Pathogenesis of bluetongue virus infection in mice, Am. J. Pathol. 68:1–15 (1972).Google Scholar
  83. 81.
    O. Narayan, H. F. McFarland, and R. T. Johnson, Effects of viral infection on nervous system development. II. Attempts to modify bluetongue virus-induced malformations with cyclophosphamide and antithymocyte serum, Am. J. Pathol. 68:15–22 (1972).Google Scholar
  84. 82.
    R. T. Johnson, K. P. Johnson, and C. J. Edmonds, Virus-induced hydrocephalus: Development of aqueductal stenosis in hamsters after mumps infection, Science (Wash. D.C.) 157:1066–1067 (1967).CrossRefGoogle Scholar
  85. 83.
    R. T. Johnson and K. P. Johnson, Hydrocephalus following viral infection: The pathology of aqueductal stenosis developing after experimental mumps virus infection, J. Neuropathol. Exp. Neurol. 27:591–606 (1968).CrossRefGoogle Scholar
  86. 84.
    R. T. Johnson and K. P. Johnson, Hydrocephalus as a sequela of experimental myxovirus infections, Exp. Mol. Pathol. 10:68–80 (1969).CrossRefGoogle Scholar
  87. 85.
    K. P. Johnson and R. T. Johnson, Granular ependymitis: Occurrence in myxovirus infected rodents and prevalence in man, Am. J. Pathol. 67:511–526 (1972).Google Scholar
  88. 86.
    L. Kilham and G. Margolis, Hydrocephalus in hamsters, ferrets, rats, and mice following inoculations with reovirus type 1.I. Virologic studies, Lab. Invest. 21:183–188 (1969).Google Scholar
  89. 87.
    G. Margolis and L. Kilham, Hydrocephalus in hamsters, ferrets, rats, and mice following inoculations with reovirus type 1. II. Pathologic studies, Lab. Invest. 21:189–198 (1969).Google Scholar
  90. 88.
    G. Margolis and L. Kilham, Experimental virus-induced hydrocephalus: Relation to pathogenesis of the Arnold-Chiari malformation, J. Neurosurg. 31:1–9 (1969).CrossRefGoogle Scholar
  91. 88a.
    F. A. Murphy, C. A. Mims, J. D. Marshall, and W. P. Taylor, Pathogenesis of non-neuronotropic arbovirus infection in mice, p. 239, abstracts, American Society for Microbiology, Annual Meeting (1972).Google Scholar
  92. 89.
    J. L. Emerson and A. L. Delez, Cerebellar hypoplasia, hypomyelinogenesis, and congenital tremors of pigs associated with prenatal vaccination of sows, J. Am. Vet. Med. Assoc. 147:47–54, 1965.Google Scholar
  93. 90.
    K. P. Johnson and D. P. Byington, Hog cholera virus: Multiple malformations produced by persistent, tolerant infection of fetal swine, Teratology 5:259 (1972).CrossRefGoogle Scholar
  94. 91.
    K. P. Johnson and D. P. Byington, Microcephaly, cerebellar hypoplasia, and hypomyelinogenesis in fetal swine persistently infected with hog cholera virus, abstract, American Association of Neuropathologists, Annual Meeting, June 1973.Google Scholar
  95. 92.
    N. H. Levitt, W. T. London, S. G. Kent, and J. L. Sever, In utero induction of cataracts and hydrocephalus in rhesus monkeys using Venezuelan equine encephalitis virus, presented at the Annual Meeting of the American Society for Microbiology, Miami Beach, May 1973.Google Scholar
  96. 93.
    F. Wenger, Necrosis cerebral masiva del feto en casos de encefalitis equina Venezulano, Invest. Clin. (Maracaibo) 21:13–21 (1967).Google Scholar
  97. 94.
    G. A. Cole, D. H. Gilden, A. A. Monjan, and N. Nathanson, Lymphocytic choriomeningitis virus: Pathogenesis of acute central nervous system disease, Fed. Proc. 30:1831–1841 (1971).Google Scholar
  98. 95.
    J. Hotchin and H. Weigand, The effect of pretreatment with X-rays on the pathogenesis of lymphocytic choriomeningitis in mice. I. Host survival, virus multiplication and leukocytosis, J. Immunol. 87:675–681 (1961).Google Scholar
  99. 96.
    V. H. Haas and S. E. Stewart, Sparing effect of A-methopterin and Guanazolo in mice infected with virus of lymphocytic choriomeningitis, Virology 2:511–516 (1956).CrossRefGoogle Scholar
  100. 97.
    J. H. Larsen, The effect of immunosuppressive therapy on murine lymphocytic choriomeningitis infection, Acta Pathol. Microbiol. Scand. 77:433–446 (1969).CrossRefGoogle Scholar
  101. 98.
    J. Hotchin and M. Cinits, Lymphocytic choriomeningitis infection of mice as a model for the study of latent virus infection, Can. J. Microbiol. 4:149–163 (1958).CrossRefGoogle Scholar
  102. 99.
    J. East, D. M. V. Parrott, and J. Seamer, The ability of mice thymectomized at birth to survive infection with lymphocytic choriomeningitis virus, Virology 22:160–162 (1964).CrossRefGoogle Scholar
  103. 100.
    A. W. Gledhill, Protective effect of anti-lymphocyte serum on murine lymphocytic choriomeningitis, Nature (Lond.) 214:178–179 (1967).CrossRefGoogle Scholar
  104. 101.
    M. S. Hirsch, F. A. Murphy, H. P. Russe, and M. D. Hicklin, Effects of thymocyte serum on lymphocytic choriomeningitis virus infection in mice, Proc. Soc. Exp. Biol. Med. 125:980–983 (1967).Google Scholar
  105. 102.
    J. Hotchin and D. Collins, Glomerulonephritis and late onset disease of mice following neonatal virus infection, Nature (Lond.) 203:1357–1359 (1964).CrossRefGoogle Scholar
  106. 103.
    M. B. A. Oldstone and F. J. Dixon, Lymphocytic choriomeningitis: Production of antibody by “tolerant” infected mice, Science (Wash. D.C.) 158:1193–1195 (1967).CrossRefGoogle Scholar
  107. 104.
    M. B. A. Oldstone and F. J. Dixon, Pathogenesis of chronic disease associated with persistent lymphocytic choriomeningitis viral infection. I. Relationship of antibody production to disease in neonatally infected mice, J. Exp. Med. 129:483–505 (1969).CrossRefGoogle Scholar
  108. 105.
    J. G. Wilson, Experimental studies on congenital malformation, J. Chron. Dis. 10:111–130 (1959).CrossRefGoogle Scholar
  109. 106.
    D. B. Singer, A. J. Rudolph, H. S. Rosenberg, W. E. Rawls, and M. Boniuk, Pathology of the congenital rubella syndrome, J. Pediatr. 71:665–675 (1967).CrossRefGoogle Scholar
  110. 107.
    R. T. Johnson and C. A. Mims, Pathogenesis of viral infections of the nervous system, N. Engl. J. Med. 278:23–30, 84-92 (1968).CrossRefGoogle Scholar
  111. 108.
    W. A. Woods, R. T. Johnson, D. C. Hostetler, M. L. Lepow, and F. C. Robbins, Immunofluorescent studies on rubella-infected tissue cultures and human tissues, J. Immunol. 96:253–260 (1966).Google Scholar
  112. 109.
    S. A. Plotkin, A. Brue, and J. E. Brue, The in vitro growth of rubella virus in human embryo cells, Am. J. Epidemiol. 81:71–85 (1965).Google Scholar
  113. 110.
    M. Boiron, J. Tanzer, M. Thomas, and A. Hampe, Early diffuse chromosome alterations in monkey kidney cells infected in vitro with herpes simplex virus, Nature (Lond.) 209:737–738 (1966).CrossRefGoogle Scholar
  114. 111.
    W. W. Michols, The role of viruses in the etiology of chromosomal abnormalities, Am. J. Hum. Genet. 18:81–92(1966).Google Scholar
  115. 112.
    J. L. Sever (ed.), Immunological responses to perinatal infection, J. Pediatr. 75:1111-1294 (1969).Google Scholar
  116. 113.
    D. Gitlin and A. Biasucci, Ontogenesis of some immunologically significant proteins in the human conceptus, Thirty-ninth Annual Meeting, Society of Pediatric Research, Atlantic City (1969).Google Scholar
  117. 114.
    R. Van Furth, H. R. E. Schutt, and W. Hijmans, The immunological development of the human fetus, J. Exp. Med. 122:1173–1188 (1965).CrossRefGoogle Scholar
  118. 115.
    A. M. Silverstein and R. J. Lukes, Fetal response to antigenic stimulus. I. Plasmacellular and lymphoid reactions in the human fetus to intrauterine infection, Lab. Invest. 11:918–932 (1962).Google Scholar
  119. 116.
    W. J. Blankenship, G. Cassady, J. Schaefer, J. V. Staumfjord, and C. A. Alford, Jr., Serum gamma-M globulin responses in acute neonatal infections and their diagnostic significance, J. Pediatr. 75:1271–1281 (1969).CrossRefGoogle Scholar
  120. 117.
    E. R. Stiehm, A. J. Ammann, and J. D. Cherry, Elevated cord macroglobulins in the diagnosis of intrauterine infections, N. Engl. J. Med. 275:971–977 (1966).CrossRefGoogle Scholar
  121. 118.
    C. A. Alford, J. Schaefer, W. J. Blankenship, J. V. Straumfjord, and G. Cassady, A correlative immunologic, microbiologie, and clinical approach to the diagnosis of acute and chronic infections in newborn infants, N. Engl. J. Med. 277:437–449 (1967).CrossRefGoogle Scholar
  122. 119.
    A. T. Scotti and L. Logan, A specific IgM antibody test in neonatal congenital syphilis, J. Pediatr. 73:242–249 (1968).CrossRefGoogle Scholar
  123. 120.
    L. Z. Cooper and S. Krugman, Clinical manifestations of postnatal and congenital rubella, Arch. Ophthal. 77:434–439 (1967).CrossRefGoogle Scholar
  124. 121.
    T. B. Tomasi, Jr., and J. Bienenstock, Secretory Immunoglobulins, Adv. Immunol. 9:1–96 (1968).CrossRefGoogle Scholar
  125. 122.
    A. C. Allison, Cell-mediated immune responses to virus infections and virus-induced tumours, Br. Med. Bull. 23:60–65 (1967).Google Scholar
  126. 123.
    R. D. A. Peterson, M. D. Cooper, and R. A. Good, The pathogenesis of immunologic deficiency states, Am. J. Med. 38:579–604 (1965).CrossRefGoogle Scholar
  127. 124.
    J. R. Montgomery, M. A. South, W. E. Rawls, J. L. Melnick, G. B. Olson, P. B. Dent, and R. A. Good, Viral inhibition of lymphocyte response to phytohemmagglutinin, Science (Wash. D.C.) 157:1068–1070 (1967).CrossRefGoogle Scholar
  128. 125.
    G. B. Olson, M. A. South, and R. A. Good, Phytohemagglutinin unresponsiveness of lymphocytes from babies with congenital rubella, Nature (Lond.) 214:695–696 (1967).CrossRefGoogle Scholar
  129. 126.
    D. A. Fuccillo, R. W. Steele, S. A. Hensen, M. M. Vincent, J. B. Hardy, and J. A. Bellanti, Impaired cellular immunity to rubella virus in congenital rubella, Inject. Immun. 9:81–84 (1974).Google Scholar
  130. 127.
    D. T. Purtilo, M. H. Hallgen, and E. J. Yunis, Depressed maternal lymphocyte response to phytohemagglutinin in human pregnancy, Lancet 1:769–771 (1972).CrossRefGoogle Scholar
  131. 128.
    V. H. Thong, R. W. Steele, M. M. Vincent, S. A. Hensen, and J. A. Bellanti, Impaired in vitro cell-mediated immunity to rubella virus during pregnancy, N. Engl. J. Med. 289:604–606 (1973).CrossRefGoogle Scholar
  132. 129.
    T. C. Merigan (ed.), Symposium on interferon and host response to virus infection, Arch. Intern. Med. 5:49–157 (1970).Google Scholar
  133. 130.
    P. I. Marcus and J. M. Salb, Molecular basis of interferon action: Inhibition of viral RNA translation, Virology 30:502–516 (1966).CrossRefGoogle Scholar
  134. 131.
    A. Isaacs, Interferon, Adv. Virus Res. 10:1–38(1963).CrossRefGoogle Scholar
  135. 132.
    A. Isaacs and S. Baron, Antiviral action of interferon in embryonic cells, Lancet 2:946–947 (1960).CrossRefGoogle Scholar
  136. 133.
    J. C. Overall and L. Glasgow, Fetal response to viral infection: Interferon production in sheep, Science (Wash. D.C.) 167:1139–1140 (1969).CrossRefGoogle Scholar
  137. 134.
    L. H. Barbosa, W. T. London, R. Hamilton, and C. Buckler, Interferon response of the rhesus monkey following viral infection, Proc. Soc. Exp. Biol. Med. 146:398–400 (1974).Google Scholar
  138. 135.
    W. E. Rawls and J. C. Melnick, Rubella virus carrier cultures derived from congenitally infected infants, J. Exp. Med. 123:795–816 (1966).CrossRefGoogle Scholar
  139. 136.
    J. Desmyter, E. W. Rawls, J. L. Melnick, M. D. Yow, and F. Barrett, Interferon in congenital rubella: Response to live attenuated measles vaccine, J. Immunol. 99:771–777 (1967).Google Scholar
  140. 137.
    J. L. Sever, Viruses and the fetus, Int. J. Gynecol. Obstet. 8:763–769 (1970).Google Scholar
  141. 138.
    J. L. Sever, Virus infections and malformations, Fed. Proc. 30:114–117 (1971).Google Scholar
  142. 139.
    Intrauterine infections, CIBA Foundation Symposium 10 (New Series) Associated Scientific Publishers, Amsterdam, London, New York (1973).Google Scholar
  143. 140.
    D. A. Fuccillo and J. L. Sever, Viral teratology, Bacteriol. Rev. 37: 19–31 (1973).Google Scholar
  144. 141.
    L. Kilham and G. Margolis, Cerebellar disease in cats induced by inoculation of rat virus, Science (Wash. D.C.) 148:244–246 (1965).CrossRefGoogle Scholar
  145. 142.
    L. Kilham and G. Margolis, Pathogenicity of minute virus of mice (MVM) for rats, mice and hamsters, Proc. Soc. Exp. Biol. Med. 133:1447–1452 (1970).Google Scholar
  146. 143.
    G. M. Ward, S. J. Roberts, K. McEntree, and J. H. Gillespie, A study of experimentally induced bovine viral diarrhea-mucosal disease in pregnant cows and their pregnancy, Cornell Vet. 59:525–538 (1969).Google Scholar
  147. 144.
    G. M. Ward, Bovine cerebellar hypoplasia apparently caused by BVD-MD virus: A case report, Cornell Vet. 59:570–576 (1969).Google Scholar
  148. 145.
    G. M. Ward, Experimental infections of pregnant sheep with bovine viral diarrhea-mucosal disease virus, Cornell Vet. 61:179–191 (1971).Google Scholar

Copyright information

© Plenum Press, New York 1975

Authors and Affiliations

  • Jerome E. Kurent
    • 1
  • John L. Sever
    • 1
  1. 1.Infectious Diseases Branch, National Institute of Neurological Diseases and StrokeNational Institutes of HealthBethesdaUSA

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