Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1984 Nov;52(2):356–363. doi: 10.1128/jvi.52.2.356-363.1984

Physical mapping of the paralysis-inducing determinant of a wild mouse ecotropic neurotropic retrovirus.

L DesGroseillers, M Barrette, P Jolicoeur
PMCID: PMC254534  PMID: 6092665

Abstract

We have recently shown that a molecularly cloned ecotropic retrovirus, initially isolated from the brain of a paralyzed wild mouse, retained the ability to induce hind limb paralysis when inoculated into susceptible mice (Jolicoeur et al., J. Virol. 45:1159-1163, 1983). To map the viral DNA sequences encoding the determinant of paralysis, we constructed chimeric viral DNA genomes in vitro between parental cloned infectious viral DNA genomes from this neurotropic murine leukemia virus (MuLV) and from nonneurotropic amphotropic 4070-A MuLV. Infectious chimeric MuLVs, recovered after microinjection of NIH 3T3 cells with these recombinant DNAs, were inoculated into newborn SIM.S and SWR/J mice to test the paralysis-inducing potential. We found that the 3.9-kilobase-pair SalI-ClaI fragment of the neurotropic MuLV comprising the 3' end of pol and all env sequences was sufficient to confer the paralysis-inducing potential to chimeric viruses. Therefore, this region of the neurotropic MuLV genome most likely harbors the primary determinant of paralysis.

Full text

PDF
356

Images in this article

359Image
on p.359
360Image
on p.360

Selected References

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

  1. Andrews J. M., Gardner M. B. Lower motor neuron degeneration associated with type C RNA virus infection in mice: neuropathological features. J Neuropathol Exp Neurol. 1974 Apr;33(2):285–307. doi: 10.1097/00005072-197404000-00007. [DOI] [PubMed] [Google Scholar]
  2. Brooks B. R., Swarz J. R., Narayan O., Johnson R. T. Murine neurotropic retrovirus spongiform polioencephalomyelopathy: acceleration of disease by virus inoculum concentration. Infect Immun. 1979 Feb;23(2):540–544. doi: 10.1128/iai.23.2.540-544.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bryant M. L., Pal B. K., Gardner M. B., Elder J. H., Jensen F. C., Lerner R. A. Structural analysis of the major envelope glycoprotein (gp70) of the amphotropic and ecotropic type C viruses of wild mice. Virology. 1978 Feb;84(2):348–358. doi: 10.1016/0042-6822(78)90254-4. [DOI] [PubMed] [Google Scholar]
  4. Chatis P. A., Holland C. A., Hartley J. W., Rowe W. P., Hopkins N. Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4408–4411. doi: 10.1073/pnas.80.14.4408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chattopadhyay S. K., Oliff A. I., Linemeyer D. L., Lander M. R., Lowy D. R. Genomes of murine leukemia viruses isolated from wild mice. J Virol. 1981 Sep;39(3):777–791. doi: 10.1128/jvi.39.3.777-791.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DesGroseillers L., Jolicoeur P. Physical mapping of the Fv-1 tropism host range determinant of BALB/c murine leukemia viruses. J Virol. 1983 Dec;48(3):685–696. doi: 10.1128/jvi.48.3.685-696.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DesGroseillers L., Rassart E., Jolicoeur P. Thymotropism of murine leukemia virus is conferred by its long terminal repeat. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4203–4207. doi: 10.1073/pnas.80.14.4203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Elder J. H., Jensen F. C., Bryant M. L., Lerner R. A. Polymorphism of the major envelope glycoprotein (gp70) of murine C-type viruses: virion associated and differentiation antigens encoded by a multi-gene family. Nature. 1977 May 5;267(5606):23–28. doi: 10.1038/267023a0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Gardner M. B. Type C viruses of wild mice: characterization and natural history of amphotropic, ecotropic, and xenotropic MuLv. Curr Top Microbiol Immunol. 1978;79:215–259. doi: 10.1007/978-3-642-66853-1_5. [DOI] [PubMed] [Google Scholar]
  11. Grandgenett D. P., Vora A. C., Schiff R. D. A 32,000-dalton nucleic acid-binding protein from avian retravirus cores possesses DNA endonuclease activity. Virology. 1978 Aug;89(1):119–132. doi: 10.1016/0042-6822(78)90046-6. [DOI] [PubMed] [Google Scholar]
  12. Grunstein M., Hogness D. S. Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proc Natl Acad Sci U S A. 1975 Oct;72(10):3961–3965. doi: 10.1073/pnas.72.10.3961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Haase A. T. The slow infection caused by visna virus. Curr Top Microbiol Immunol. 1975;72:101–156. doi: 10.1007/978-3-642-66289-8_4. [DOI] [PubMed] [Google Scholar]
  14. Hartley J. W., Rowe W. P. Naturally occurring murine leukemia viruses in wild mice: characterization of a new "amphotropic" class. J Virol. 1976 Jul;19(1):19–25. doi: 10.1128/jvi.19.1.19-25.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hoffman P. M., Davidson W. F., Ruscetti S. K., Chused T. M., Morse H. C., 3rd Wild mouse ecotropic murine leukemia virus infection of inbred mice: dual-tropic virus expression precedes the onset of paralysis and lymphoma. J Virol. 1981 Aug;39(2):597–602. doi: 10.1128/jvi.39.2.597-602.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jolicoeur P., Baltimore D. Effect of Fv-1 gene product on proviral DNA formation and integration in cells infected with murine leukemia viruses. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2236–2240. doi: 10.1073/pnas.73.7.2236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jolicoeur P., Nicolaiew N., DesGroseillers L., Rassart E. Molecular cloning of infectious viral DNA from ecotropic neurotropic wild mouse retrovirus. J Virol. 1983 Mar;45(3):1159–1163. doi: 10.1128/jvi.45.3.1159-1163.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jolicoeur P., Rassart E. Effect of Fv-1 gene product on synthesis of linear and supercoiled viral DNA in cells infected with murine leukemia virus. J Virol. 1980 Jan;33(1):183–195. doi: 10.1128/jvi.33.1.183-195.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Keshet E., Temin H. M. Cell killing by spleen necrosis virus is correlated with a transient accumulation of spleen necrosis virus DNA. J Virol. 1979 Aug;31(2):376–388. doi: 10.1128/jvi.31.2.376-388.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lai M. M., Shimizu C. S., Rasheed S., Pal B. K., Gardner M. B. Characterization of genome structure of amphotropic and ecotropic wild mouse retroviruses. J Virol. 1982 Feb;41(2):605–614. doi: 10.1128/jvi.41.2.605-614.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Officer J. E., Tecson N., Estes J. D., Fontanilla E., Rongey R. W., Gardner M. B. Isolation of a neurotropic type C virus. Science. 1973 Sep 7;181(4103):945–947. doi: 10.1126/science.181.4103.945. [DOI] [PubMed] [Google Scholar]
  22. Oldstone M. B., Jensen F., Dixon F. J., Lampert P. W. Pathogenesis of the slow disease of the central nervous system associated with wild mouse virus. II. Role of virus and host gene products. Virology. 1980 Nov;107(1):180–193. doi: 10.1016/0042-6822(80)90283-4. [DOI] [PubMed] [Google Scholar]
  23. Oldstone M. B., Jensen F., Elder J., Dixon F. J., Lampert P. W. Pathogenesis of the slow disease of the central nervous system associated with wild mouse virus. III. Role of input virus and MCF recombinants in disease. Virology. 1983 Jul 15;128(1):154–165. doi: 10.1016/0042-6822(83)90326-4. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Papkoff J., Verma I. M., Hunter T. Detection of a transforming gene product in cells transformed by Moloney murine sarcoma virus. Cell. 1982 Jun;29(2):417–426. doi: 10.1016/0092-8674(82)90158-1. [DOI] [PubMed] [Google Scholar]
  26. Rasheed S., Gardner M. B., Chan E. Amphotropic host range of naturally occuring wild mouse leukemia viruses. J Virol. 1976 Jul;19(1):13–18. doi: 10.1128/jvi.19.1.13-18.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rassart E., Jolicoeur P. Restriction endonuclease mapping of unintegrated viral DNA of B- and N-tropic BALB/c murine leukemia virus. J Virol. 1980 Sep;35(3):812–823. doi: 10.1128/jvi.35.3.812-823.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  29. Rowe W. P., Pugh W. E., Hartley J. W. Plaque assay techniques for murine leukemia viruses. Virology. 1970 Dec;42(4):1136–1139. doi: 10.1016/0042-6822(70)90362-4. [DOI] [PubMed] [Google Scholar]
  30. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  31. Storms R. K., Holowachuck E. W., Friesen J. D. Genetic complementation of the Saccharomyces cerevisiae leu2 gene by the Escherichia coli leuB gene. Mol Cell Biol. 1981 Sep;1(9):836–842. doi: 10.1128/mcb.1.9.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sveda M. M., Soeiro R. Host restriction of Friend leukemia virus: synthesis and integration of the provirus. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2356–2360. doi: 10.1073/pnas.73.7.2356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ware L. M., Axelrad A. A. Inherited resistance to N- and B-tropic murine leukemia viruses in vitro: evidence that congenic mouse strains SIM and SIM.R differ at the Fv-1 locus. Virology. 1972 Nov;50(2):339–348. doi: 10.1016/0042-6822(72)90385-6. [DOI] [PubMed] [Google Scholar]
  34. Weller S. K., Temin H. M. Cell killing by avian leukosis viruses. J Virol. 1981 Sep;39(3):713–721. doi: 10.1128/jvi.39.3.713-721.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wong P. K., Soong M. M., MacLeod R., Gallick G. E., Yuen P. H. A group of temperature-sensitive mutants of Moloney leukemia virus which is defective in cleavage of env precursor polypeptide in infected cells also induces hind-limb paralysis in newborn CFW/D mice. Virology. 1983 Mar;125(2):513–518. doi: 10.1016/0042-6822(83)90225-8. [DOI] [PubMed] [Google Scholar]
  36. Ziegler S. F., Whitlock C. A., Goff S. P., Gifford A., Witte O. N. Lethal effect of the Abelson murine leukemia virus transforming gene product. Cell. 1981 Dec;27(3 Pt 2):477–486. doi: 10.1016/0092-8674(81)90389-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES