Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1995 Dec;69(12):8070–8075. doi: 10.1128/jvi.69.12.8070-8075.1995

Characterization of a neurologic disease induced by a polytropic murine retrovirus: evidence for differential targeting of ecotropic and polytropic viruses in the brain.

J L Portis 1, S Czub 1, S Robertson 1, F McAtee 1, B Chesebro 1
PMCID: PMC189756  PMID: 7494324

Abstract

A variety of ecotropic murine leukemia viruses cause neurodegenerative disease. We describe here the clinical and histopathological features of a neurologic disease induced by a polytropic murine leukemia virus, FMCF98. Clinical disease was dominated by hyperexcitability and ataxia, and the histopathology was characterized primarily by astrocytosis and astrocytic degeneration. The viral envelope gene harbored the determinants of neurovirulence, since the chimeric virus Fr98E, which contained the envelope gene of FMCF98 on a background of the nonneurovirulent virus FB29, caused a similar disease. The disease caused by Fr98E differed from that induced by the coisogenic neurovirulent ecotropic virus FrCasE in clinical presentation, histopathology, and distribution of virus in the central nervous system. Since Fr98E contains a polytropic envelope gene and FrCasE contains an ecotropic envelope gene, these phenotypic differences appeared to be determined by envelope sequences and may reflect differences in virus receptor usage in the central nervous system.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  1. Baszler T. V., Whiteley H. E., Zachary J. F. Ocular infection with a murine neurovirulent retrovirus does not cause retinal degeneration. Invest Ophthalmol Vis Sci. 1992 Feb;33(2):384–389. [PubMed] [Google Scholar]
  2. Baszler T. V., Zachary J. F. Murine retroviral neurovirulence correlates with an enhanced ability ofvirus to infect selectively, replicate in, and activate resident microglial cells. Am J Pathol. 1991 Mar;138(3):655–671. [PMC free article] [PubMed] [Google Scholar]
  3. Bilello J. A., Pitts O. M., Hoffman P. M. Characterization of a progressive neurodegenerative disease induced by a temperature-sensitive Moloney murine leukemia virus infection. J Virol. 1986 Aug;59(2):234–241. doi: 10.1128/jvi.59.2.234-241.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brooks B. R., Swarz J. R., Johnson R. T. Spongiform polioencephalomyelopathy caused by a murine retrovirus. I. Pathogenesis of infection in newborn mice. Lab Invest. 1980 Nov;43(5):480–486. [PubMed] [Google Scholar]
  5. Buller R. S., Wehrly K., Portis J. L., Chesebro B. Host genes conferring resistance to a central nervous system disease induced by a polytropic recombinant Friend murine retrovirus. J Virol. 1990 Feb;64(2):493–498. doi: 10.1128/jvi.64.2.493-498.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Campbell I. L., Abraham C. R., Masliah E., Kemper P., Inglis J. D., Oldstone M. B., Mucke L. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10061–10065. doi: 10.1073/pnas.90.21.10061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chesebro B., Wehrly K. Different murine cell lines manifest unique patterns of interference to superinfection by murine leukemia viruses. Virology. 1985 Feb;141(1):119–129. doi: 10.1016/0042-6822(85)90188-6. [DOI] [PubMed] [Google Scholar]
  8. Czub M., McAtee F. J., Czub S., Lynch W. P., Portis J. L. Prevention of retrovirus-induced neurological disease by infection with a nonneuropathogenic retrovirus. Virology. 1995 Jan 10;206(1):372–380. doi: 10.1016/s0042-6822(95)80052-2. [DOI] [PubMed] [Google Scholar]
  9. Czub S., Lynch W. P., Czub M., Portis J. L. Kinetic analysis of spongiform neurodegenerative disease induced by a highly virulent murine retrovirus. Lab Invest. 1994 May;70(5):711–723. [PubMed] [Google Scholar]
  10. DesGroseillers L., Barrette M., Jolicoeur P. Physical mapping of the paralysis-inducing determinant of a wild mouse ecotropic neurotropic retrovirus. J Virol. 1984 Nov;52(2):356–363. doi: 10.1128/jvi.52.2.356-363.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eddleston M., Mucke L. Molecular profile of reactive astrocytes--implications for their role in neurologic disease. Neuroscience. 1993 May;54(1):15–36. doi: 10.1016/0306-4522(93)90380-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gardner M. B., Henderson B. E., Officer J. E., Rongey R. W., Parker J. C., Oliver C., Estes J. D., Huebner R. J. A spontaneous lower motor neuron disease apparently caused by indigenous type-C RNA virus in wild mice. J Natl Cancer Inst. 1973 Oct;51(4):1243–1254. doi: 10.1093/jnci/51.4.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Giulian D., Li J., Li X., George J., Rutecki P. A. The impact of microglia-derived cytokines upon gliosis in the CNS. Dev Neurosci. 1994;16(3-4):128–136. doi: 10.1159/000112099. [DOI] [PubMed] [Google Scholar]
  14. Giulian D., Vaca K., Noonan C. A. Secretion of neurotoxins by mononuclear phagocytes infected with HIV-1. Science. 1990 Dec 14;250(4987):1593–1596. doi: 10.1126/science.2148832. [DOI] [PubMed] [Google Scholar]
  15. Glass J. D., Wesselingh S. L., Selnes O. A., McArthur J. C. Clinical-neuropathologic correlation in HIV-associated dementia. Neurology. 1993 Nov;43(11):2230–2237. doi: 10.1212/wnl.43.11.2230. [DOI] [PubMed] [Google Scholar]
  16. Gravel C., Kay D. G., Jolicoeur P. Identification of the infected target cell type in spongiform myeloencephalopathy induced by the neurotropic Cas-Br-E murine leukemia virus. J Virol. 1993 Nov;67(11):6648–6658. doi: 10.1128/jvi.67.11.6648-6658.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hoffman P. M., Cimino E. F., Robbins D. S., Broadwell R. D., Powers J. M., Ruscetti S. K. Cellular tropism and localization in the rodent nervous system of a neuropathogenic variant of Friend murine leukemia virus. Lab Invest. 1992 Sep;67(3):314–321. [PubMed] [Google Scholar]
  18. Johnson R. T., McArthur J. C., Narayan O. The neurobiology of human immunodeficiency virus infections. FASEB J. 1988 Nov;2(14):2970–2981. doi: 10.1096/fasebj.2.14.2846395. [DOI] [PubMed] [Google Scholar]
  19. Kai K., Furuta T. Isolation of paralysis-inducing murine leukemia viruses from Friend virus passaged in rats. J Virol. 1984 Jun;50(3):970–973. doi: 10.1128/jvi.50.3.970-973.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kay D. G., Gravel C., Robitaille Y., Jolicoeur P. 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 U S A. 1991 Feb 15;88(4):1281–1285. doi: 10.1073/pnas.88.4.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lynch W. P., Czub S., McAtee F. J., Hayes S. F., Portis J. L. Murine retrovirus-induced spongiform encephalopathy: productive infection of microglia and cerebellar neurons in accelerated CNS disease. Neuron. 1991 Sep;7(3):365–379. doi: 10.1016/0896-6273(91)90289-c. [DOI] [PubMed] [Google Scholar]
  22. Lynch W. P., Portis J. L. Murine retrovirus-induced spongiform encephalopathy: disease expression is dependent on postnatal development of the central nervous system. J Virol. 1993 May;67(5):2601–2610. doi: 10.1128/jvi.67.5.2601-2610.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lynch W. P., Robertson S. J., Portis J. L. Induction of focal spongiform neurodegeneration in developmentally resistant mice by implantation of murine retrovirus-infected microglia. J Virol. 1995 Mar;69(3):1408–1419. doi: 10.1128/jvi.69.3.1408-1419.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Masuda M., Hoffman P. M., Ruscetti S. K. Viral determinants that control the neuropathogenicity of PVC-211 murine leukemia virus in vivo determine brain capillary endothelial cell tropism of the virus in vitro. J Virol. 1993 Aug;67(8):4580–4587. doi: 10.1128/jvi.67.8.4580-4587.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Oldstone M. B., Lampert P. W., Lee S., Dixon F. J. Pathogenesis of the slow disease of the central nervous system associated with WM 1504 E virus. I. Relationship of strain susceptibility and replication to disease. Am J Pathol. 1977 Jul;88(1):193–212. [PMC free article] [PubMed] [Google Scholar]
  26. Portis J. L., Czub S., Garon C. F., McAtee F. J. Neurodegenerative disease induced by the wild mouse ecotropic retrovirus is markedly accelerated by long terminal repeat and gag-pol sequences from nondefective Friend murine leukemia virus. J Virol. 1990 Apr;64(4):1648–1656. doi: 10.1128/jvi.64.4.1648-1656.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Portis J. L., Spangrude G. J., McAtee F. J. Identification of a sequence in the unique 5' open reading frame of the gene encoding glycosylated Gag which influences the incubation period of neurodegenerative disease induced by a murine retrovirus. J Virol. 1994 Jun;68(6):3879–3887. doi: 10.1128/jvi.68.6.3879-3887.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Portis J. L. Wild mouse retrovirus: pathogenesis. Curr Top Microbiol Immunol. 1990;160:11–27. doi: 10.1007/978-3-642-75267-4_2. [DOI] [PubMed] [Google Scholar]
  29. Rein A. Interference grouping of murine leukemia viruses: a distinct receptor for the MCF-recombinant viruses in mouse cells. Virology. 1982 Jul 15;120(1):251–257. doi: 10.1016/0042-6822(82)90024-1. [DOI] [PubMed] [Google Scholar]
  30. Robertson M. N., Miyazawa M., Mori S., Caughey B., Evans L. H., Hayes S. F., Chesebro B. Production of monoclonal antibodies reactive with a denatured form of the Friend murine leukemia virus gp70 envelope protein: use in a focal infectivity assay, immunohistochemical studies, electron microscopy and western blotting. J Virol Methods. 1991 Oct;34(3):255–271. doi: 10.1016/0166-0934(91)90105-9. [DOI] [PubMed] [Google Scholar]
  31. Selmaj K. W., Farooq M., Norton W. T., Raine C. S., Brosnan C. F. Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. J Immunol. 1990 Jan 1;144(1):129–135. [PubMed] [Google Scholar]
  32. Sitbon M., Nishio J., Wehrly K., Lodmell D., Chesebro B. Use of a focal immunofluorescence assay on live cells for quantitation of retroviruses: distinction of host range classes in virus mixtures and biological cloning of dual-tropic murine leukemia viruses. Virology. 1985 Feb;141(1):110–118. doi: 10.1016/0042-6822(85)90187-4. [DOI] [PubMed] [Google Scholar]
  33. Sitbon M., Sola B., Evans L., Nishio J., Hayes S. F., Nathanson K., Garon C. F., Chesebro B. Hemolytic anemia and erythroleukemia, two distinct pathogenic effects of Friend MuLV: mapping of the effects to different regions of the viral genome. Cell. 1986 Dec 26;47(6):851–859. doi: 10.1016/0092-8674(86)90800-7. [DOI] [PubMed] [Google Scholar]
  34. Szurek P. F., Yuen P. H., Ball J. K., Wong P. K. A Val-25-to-Ile substitution in the envelope precursor polyprotein, gPr80env, is responsible for the temperature sensitivity, inefficient processing of gPr80env, and neurovirulence of ts1, a mutant of Moloney murine leukemia virus TB. J Virol. 1990 Feb;64(2):467–475. doi: 10.1128/jvi.64.2.467-475.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tyor W. R., Glass J. D., Griffin J. W., Becker P. S., McArthur J. C., Bezman L., Griffin D. E. Cytokine expression in the brain during the acquired immunodeficiency syndrome. Ann Neurol. 1992 Apr;31(4):349–360. doi: 10.1002/ana.410310402. [DOI] [PubMed] [Google Scholar]
  36. Wong P. K. Moloney murine leukemia virus temperature-sensitive mutants: a model for retrovirus-induced neurologic disorders. Curr Top Microbiol Immunol. 1990;160:29–60. doi: 10.1007/978-3-642-75267-4_3. [DOI] [PubMed] [Google Scholar]
  37. Zachary J. F., Knupp C. J., Wong P. K. Noninflammatory spongiform polioencephalomyelopathy caused by a neurotropic temperature-sensitive mutant of Moloney murine leukemia virus TB. Am J Pathol. 1986 Sep;124(3):457–468. [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES