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. 1987 Jun;61(6):1919–1926. doi: 10.1128/jvi.61.6.1919-1926.1987

Identification of a nonproductive, cell-associated form of measles virus by its resistance to inhibition by recombinant human interferon.

D R Carrigan, C M Kabacoff
PMCID: PMC254199  PMID: 3573153

Abstract

Subacute sclerosing panencephalitis (SSPE) is a fatal disease in children and young adults that is caused by persistent infection of the central nervous system (CNS) by a nonproductive, cell-associated form of measles virus. Using an experimental model for SSPE (LEC viral strain in newborn hamsters), we have shown previously that establishment of such CNS infections involves selective elimination from the CNS of productively infected cells by host defensive mechanisms, coupled with the selective sparing of cells carrying nonproductive viral forms. That interferon (IFN) may play a role in this process was suggested by the disappearance of productively infected cells from the CNS tissues prior to the appearance of antiviral antibodies and by the demonstration of cell-associated, IFN-resistant viral variants in the virus stocks that were used. Results of this study support these conclusions by showing that similar IFN-resistant viral variants are present in the HBS strain of SSPE-derived measles virus and that these variants, in the presence of IFN, have properties that are similar to those of naturally occurring cell-associated strains of SSPE viruses, e.g., DR, IP3, and Biken. These IFN-resistant forms of HBS virus were isolated and were shown to maintain their resistance to inhibition by IFN after cloning. However, on removal of IFN, they reverted to productive forms similar to the parental HBS virus. The potential role of such viral forms in the pathogenesis of SSPE is discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aaby P., Bukh J., Lisse I. M., Smits A. J. Risk factors in subacute sclerosing panencephalitis: age- and sex-dependent host reactions or intensive exposure? Rev Infect Dis. 1984 Mar-Apr;6(2):239–250. doi: 10.1093/clinids/6.2.239. [DOI] [PubMed] [Google Scholar]
  2. Abbott R. J., Bolderson I., Gruer P. J. IFN-gamma and IFN-alpha in CSF in viral meningitis. Lancet. 1985 Aug 24;2(8452):456–457. doi: 10.1016/s0140-6736(85)92784-9. [DOI] [PubMed] [Google Scholar]
  3. Allen L. B., Eagle N. C., Huffman J. H., Shuman D. A., Meyer R. B., Jr, Sidwell R. W. Enhancement of interferon antiviral action in L-cells by cyclic nucleotides. Proc Soc Exp Biol Med. 1974 Jun;146(2):580–584. doi: 10.3181/00379727-146-38151. [DOI] [PubMed] [Google Scholar]
  4. Barbanti-Brodano G., Oyanagi S., Katz M., Koprowski H. Presence of 2 different viral agents in brain cells of patients with subacute sclerosing panencephalitis. Proc Soc Exp Biol Med. 1970 May;134(1):230–236. doi: 10.3181/00379727-134-34765. [DOI] [PubMed] [Google Scholar]
  5. Bartram C. R., Henke J., Treuner J., Basler M., Esch A., Mortier W. Subacute sclerosing panencephalitis in a brother and sister. Therapeutic trial of fibroblast interferon. Eur J Pediatr. 1982 Mar;138(2):187–190. doi: 10.1007/BF00441152. [DOI] [PubMed] [Google Scholar]
  6. Behan P. O. Interferon in treatment of subacute sclerosing panencephalitis. Lancet. 1981 May 9;1(8228):1059–1060. doi: 10.1016/s0140-6736(81)92228-5. [DOI] [PubMed] [Google Scholar]
  7. Burnstein T., Jacobsen L. B., Zeman W., Chen T. T. Persistent infection of BSC-1 cells by defective measles virus derived from subacute sclerosing panencephalitis. Infect Immun. 1974 Dec;10(6):1378–1382. doi: 10.1128/iai.10.6.1378-1382.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bye A., Balkwill F., Brigden D., Wilson J. Use of interferon in the management of patients with subacute sclerosing panencephalitis. Dev Med Child Neurol. 1985 Apr;27(2):170–175. doi: 10.1111/j.1469-8749.1985.tb03766.x. [DOI] [PubMed] [Google Scholar]
  9. Byington D. P., Castro A. E., Burnstein T. Adaptation to hamsters of neurotropic measles virus from subacute sclerosing panencephalitis. Nature. 1970 Feb 7;225(5232):554–555. doi: 10.1038/225554b0. [DOI] [PubMed] [Google Scholar]
  10. Carrigan D. R., Kabacoff C. M. Nonproductive, cell-associated virus exists before the appearance of antiviral antibodies in experimental measles encephalitis. Virology. 1987 Jan;156(1):185–188. doi: 10.1016/0042-6822(87)90452-1. [DOI] [PubMed] [Google Scholar]
  11. Carrigan D. R. Round cell variant of measles virus: mechanisms involved in the establishment of defective viral infection of the central nervous system. Virology. 1986 Dec;155(2):614–624. doi: 10.1016/0042-6822(86)90221-7. [DOI] [PubMed] [Google Scholar]
  12. Carrigan D. R. Round cell variant of measles virus: neurovirulence and pathogenesis of acute encephalitis in newborn hamsters. Virology. 1986 Jan 30;148(2):349–359. doi: 10.1016/0042-6822(86)90331-4. [DOI] [PubMed] [Google Scholar]
  13. Carrigan D. R. Round cell variant of measles virus: spontaneous conversion from productive to cell-associated state of infection. Virology. 1985 Jul 30;144(2):337–350. doi: 10.1016/0042-6822(85)90276-4. [DOI] [PubMed] [Google Scholar]
  14. Clemens M. J., McNurlan M. A. Regulation of cell proliferation and differentiation by interferons. Biochem J. 1985 Mar 1;226(2):345–360. doi: 10.1042/bj2260345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Doi Y., Sanpe T., Nakajima M., Okawa S., Koto T. Properties of a cytopathic agent isolated from a patient with subacute sclerosing panencephalitis in Japan. Jpn J Med Sci Biol. 1972 Oct;25(5):321–333. doi: 10.7883/yoken1952.25.321. [DOI] [PubMed] [Google Scholar]
  16. Haase A. T., Gantz D., Eble B., Walker D., Stowring L., Ventura P., Blum H., Wietgrefe S., Zupancic M., Tourtellotte W. Natural history of restricted synthesis and expression of measles virus genes in subacute sclerosing panencephalitis. Proc Natl Acad Sci U S A. 1985 May;82(9):3020–3024. doi: 10.1073/pnas.82.9.3020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Haase A. T., Stowring L., Ventura P., Burks J., Ebers G., Tourtellotte W., Warren K. Detection by hybridization of viral infection of the human central nervous system. Ann N Y Acad Sci. 1984;436:103–108. doi: 10.1111/j.1749-6632.1984.tb14780.x. [DOI] [PubMed] [Google Scholar]
  18. Heremans H., de Ley M., Volckaert-Vervliet G., Billiau A. Interferon production and virus replication in lymphoblastoid cells infected with different viruses. Arch Virol. 1980;63(3-4):317–320. doi: 10.1007/BF01315039. [DOI] [PubMed] [Google Scholar]
  19. Hilfenhaus J., Ackermann R. Endogenous interferon in the cerebrospinal fluid of herpes encephalitis patients. Proc Soc Exp Biol Med. 1981 Feb;166(2):205–209. doi: 10.3181/00379727-166-41047. [DOI] [PubMed] [Google Scholar]
  20. Horta-Barbosa L., Fuccillo D. A., Sever J. L., Zeman W. Subacute sclerosing panencephalitis: isolation of measles virus from a brain biopsy. Nature. 1969 Mar 8;221(5184):974–974. doi: 10.1038/221974a0. [DOI] [PubMed] [Google Scholar]
  21. Hänninen P., Arstila P., Lang H., Salmi A., Panelius M. Involvement of the central nervous system in acute, uncomplicated measles virus infection. J Clin Microbiol. 1980 Jun;11(6):610–613. doi: 10.1128/jcm.11.6.610-613.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Iwasaki Y., Koprowski H. Cell to cell transmission of virus in the central nervous system. I. Subacute sclerosing panencephalitis. Lab Invest. 1974 Aug;31(2):187–196. [PubMed] [Google Scholar]
  23. Jacobson S., McFarland H. F. Measles virus persistence in human lymphocytes: a role for virus-induced interferon. J Gen Virol. 1982 Dec;63(2):351–357. doi: 10.1099/0022-1317-63-2-351. [DOI] [PubMed] [Google Scholar]
  24. Johnson K. P., Norrby E. Subacute sclerosing panencephalitis (SSPE) agent in hamsters. 3. Induction of defective measles infection in hamster brain. Exp Mol Pathol. 1974 Oct;21(2):166–178. doi: 10.1016/0014-4800(74)90087-2. [DOI] [PubMed] [Google Scholar]
  25. Johnson K. P., Norrby E., Swoveland P., Carrigan D. R. Experimental subacute sclerosing panencephalitis: selective disappearance of measles virus matrix protein from the Central nervous system. J Infect Dis. 1981 Aug;144(2):161–169. doi: 10.1093/infdis/144.2.161. [DOI] [PubMed] [Google Scholar]
  26. Johnson K. P., Norrby E., Swoveland P., Carrigan D. R. Expression of five viral antigens in cells infected with wild-type and SSPE strains of measles virus: correlation with cytopathic effects and productivity of infections. Arch Virol. 1982;73(3-4):255–262. doi: 10.1007/BF01318079. [DOI] [PubMed] [Google Scholar]
  27. Johnson R. T., Griffin D. E., Hirsch R. L., Wolinsky J. S., Roedenbeck S., Lindo de Soriano I., Vaisberg A. Measles encephalomyelitis--clinical and immunologic studies. N Engl J Med. 1984 Jan 19;310(3):137–141. doi: 10.1056/NEJM198401193100301. [DOI] [PubMed] [Google Scholar]
  28. Joncas J. H., Robillard L. R., Boudreault A., Leyritz M., McLaughlin B. J. Letter: Interferon in serum and cerebrospinal fluid in subacute sclerosing panencephalitis. Can Med Assoc J. 1976 Aug 21;115(4):309–309. [PMC free article] [PubMed] [Google Scholar]
  29. Kono S., Koase M., Sakata H., Shimizu Y. Variable interferon productivity of Vero cells. Brief report. Arch Gesamte Virusforsch. 1972;37(1):141–143. doi: 10.1007/BF01241159. [DOI] [PubMed] [Google Scholar]
  30. Kramer M. J., Dennin R., Kramer C., Jones G., Connell E., Rolon N., Gruarin A., Kale R., Trown P. W. Cell and virus sensitivity studies with recombinant human alpha interferons. J Interferon Res. 1983;3(4):425–435. doi: 10.1089/jir.1983.3.425. [DOI] [PubMed] [Google Scholar]
  31. Larke R. P. Interferon in the cerebrospinal fluid of children with central nervous system disorders. Can Med Assoc J. 1967 Jan 7;96(1):21–32. [PMC free article] [PubMed] [Google Scholar]
  32. Lebon P., Ponsot G., Aicardi J., Goutières F., Arthuis M. Early intrathecal synthesis of interferon in herpes encephalitis. Biomedicine. 1979 Dec;31(9-10):267–271. [PubMed] [Google Scholar]
  33. Legaspi R. C., Gatmaitan B., Bailey E. J., Lerner A. M. Interferon in biopsy and autopsy specimens of brain. Its presence in herpes simplex virus encephalitis. Arch Neurol. 1980 Feb;37(2):76–79. doi: 10.1001/archneur.1980.00500510034004. [DOI] [PubMed] [Google Scholar]
  34. McKimm J., Rapp F. Variation in ability of measles virus plaque progeny to induce interferon. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3056–3059. doi: 10.1073/pnas.74.7.3056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Miller C. A., Carrigan D. R. Reversible repression and activation of measles virus infection in neural cells. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1629–1633. doi: 10.1073/pnas.79.5.1629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Miyazu M., Morishima T., Hanada N., Isomura S., Suzuki S. Types of interferons detected in cerebrospinal fluid from patients with viral infections of the central nervous system. J Infect Dis. 1985 Nov;152(5):1098–1099. doi: 10.1093/infdis/152.5.1098a. [DOI] [PubMed] [Google Scholar]
  37. Nakagawa M., Michihata T., Yoshioka H., Sawada T., Kusunoki T., Kishida T. Intrathecal administration of human leukocyte interferon to a patient with subacute sclerosing panencephalitis. Acta Paediatr Scand. 1985 Mar;74(2):309–310. doi: 10.1111/j.1651-2227.1985.tb10973.x. [DOI] [PubMed] [Google Scholar]
  38. Norris F. H., Panitch H. S., Denys E. H., Downes K., Cantell K., Smith R. A. The treatment of subacute sclerosing panencephalitis with interferon: a case report. J Neurol. 1986 Apr;233(2):102–107. doi: 10.1007/BF00313855. [DOI] [PubMed] [Google Scholar]
  39. Panitch H. S., Gomez-Plascencia J., Norris F. H., Cantell K., Smith R. A. Subacute sclerosing panencephalitis: remission after treatment with intraventricular interferon. Neurology. 1986 Apr;36(4):562–566. doi: 10.1212/wnl.36.4.562. [DOI] [PubMed] [Google Scholar]
  40. Rager-Zisman B., Egan J. E., Kress Y., Bloom B. R. Isolation of cold-sensitive mutants of measles virus from persistently infected murine neuroblastoma cells. J Virol. 1984 Sep;51(3):845–855. doi: 10.1128/jvi.51.3.845-855.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Risk W. S., Haddad F. S., Chemali R. Substantial spontaneous long-term improvement in subacute sclerosing panencephalitis. Six cases from the Middle East and a review of the literature. Arch Neurol. 1978 Aug;35(8):494–502. doi: 10.1001/archneur.1978.00500320014004. [DOI] [PubMed] [Google Scholar]
  42. Risk W. S., Haddad F. S. The variable natural history of subacute sclerosing panencephalitis: a study of 118 cases from the Middle East. Arch Neurol. 1979 Oct;36(10):610–614. doi: 10.1001/archneur.1979.00500460044004. [DOI] [PubMed] [Google Scholar]
  43. Robbins S. J., Rapp F. Inhibition of measles virus replication by cyclic AMP. Virology. 1980 Oct 30;106(2):317–326. doi: 10.1016/0042-6822(80)90255-x. [DOI] [PubMed] [Google Scholar]
  44. Thormar H., Jervis G. A., Karl S. C., Brown H. R. Passage in ferrets of encephalitogenic cell-associated measles virus isolated from brain of a patient with subacute sclerosing panencephalitis. J Infect Dis. 1973 Jun;127(6):678–685. doi: 10.1093/infdis/127.6.678. [DOI] [PubMed] [Google Scholar]
  45. Toy J. L. The interferons. Clin Exp Immunol. 1983 Oct;54(1):1–13. [PMC free article] [PubMed] [Google Scholar]
  46. Tsai S. C., Summers B. A., Appel M. J. Interferon in cerebrospinal fluid. A marker for viral persistence of canine distemper encephalomyelitis. Arch Virol. 1982;72(4):257–265. doi: 10.1007/BF01315222. [DOI] [PubMed] [Google Scholar]
  47. Ueda S., Okuno Y., Hamamoto Y., Oya H. Subacute sclerosing panencephalitis (SSPE): isolation of a defective variant of measles virus from brain obtained at autopsy. Biken J. 1975 Jun;18(2):113–122. [PubMed] [Google Scholar]
  48. Volckaert-Vervliet G., Billiau A. Induction of interferon in human lymphoblastoid cells by Sendai and measles viruses. J Gen Virol. 1977 Oct;37(1):199–203. doi: 10.1099/0022-1317-37-1-199. [DOI] [PubMed] [Google Scholar]
  49. Weber J. M., Stewart R. B. Cyclic AMP potentiation of interferon antiviral activity and effect of interferon on cellular cyclic AMP levels. J Gen Virol. 1975 Sep;28(3):363–372. doi: 10.1099/0022-1317-28-3-363. [DOI] [PubMed] [Google Scholar]

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