Abstract
The major determinants involved in neurological disease induction by polytropic murine leukemia virus FMCF98 are encoded by the envelope gene. To map these determinants further, we produced four chimeras which contained neurovirulent FMCF98 envelope sequences combined with envelope sequences from the closely related nonneurovirulent polytropic virus FMCF54. Surprisingly, two chimeric viruses containing completely separate envelope regions from FMCF98 could both induce neurological disease. Clinical signs caused by both neurovirulent chimeras appeared to be indistinguishable from those caused by FMCF98, although the incubation periods were longer. One neurovirulence determinant mapped to the N-terminal portion of gp7O, which contains the VRA and VRB receptor-binding regions, while the other determinant mapped downstream of both of the variable regions. Western blot (immunoblot) analyses and immunohistochemical staining of tissue sections indicated that the variations in neurovirulence of these viruses could not be explained by differences in either the quantitative level or the location of virus expression in the brain.
Full Text
The Full Text of this article is available as a PDF (408.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Battini J. L., Heard J. M., Danos O. Receptor choice determinants in the envelope glycoproteins of amphotropic, xenotropic, and polytropic murine leukemia viruses. J Virol. 1992 Mar;66(3):1468–1475. doi: 10.1128/jvi.66.3.1468-1475.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Chesebro B., Wehrly K., Nishio J., Perryman S. Macrophage-tropic human immunodeficiency virus isolates from different patients exhibit unusual V3 envelope sequence homogeneity in comparison with T-cell-tropic isolates: definition of critical amino acids involved in cell tropism. J Virol. 1992 Nov;66(11):6547–6554. doi: 10.1128/jvi.66.11.6547-6554.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Czub M., McAtee F. J., Portis J. L. Murine retrovirus-induced spongiform encephalomyelopathy: host and viral factors which determine the length of the incubation period. J Virol. 1992 Jun;66(6):3298–3305. doi: 10.1128/jvi.66.6.3298-3305.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Evans L. H., Morrison R. P., Malik F. G., Portis J., Britt W. J. A neutralizable epitope common to the envelope glycoproteins of ecotropic, polytropic, xenotropic, and amphotropic murine leukemia viruses. J Virol. 1990 Dec;64(12):6176–6183. doi: 10.1128/jvi.64.12.6176-6183.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Johnson R. T., Glass J. D., McArthur J. C., Chesebro B. W. Quantitation of human immunodeficiency virus in brains of demented and nondemented patients with acquired immunodeficiency syndrome. Ann Neurol. 1996 Mar;39(3):392–395. doi: 10.1002/ana.410390319. [DOI] [PubMed] [Google Scholar]
- 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]
- Koch W., Zimmermann W., Oliff A., Friedrich R. Molecular analysis of the envelope gene and long terminal repeat of Friend mink cell focus-inducing virus: implications for the functions of these sequences. J Virol. 1984 Mar;49(3):828–840. doi: 10.1128/jvi.49.3.828-840.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lane T. E., Buchmeier M. J., Watry D. D., Jakubowski D. B., Fox H. S. Serial passage of microglial SIV results in selection of homogeneous env quasispecies in the brain. Virology. 1995 Oct 1;212(2):458–465. doi: 10.1006/viro.1995.1503. [DOI] [PubMed] [Google Scholar]
- 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]
- Masuda M., Remington M. P., Hoffman P. M., Ruscetti S. K. Molecular characterization of a neuropathogenic and nonerythroleukemogenic variant of Friend murine leukemia virus PVC-211. J Virol. 1992 May;66(5):2798–2806. doi: 10.1128/jvi.66.5.2798-2806.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McAtee F. J., Portis J. L. Monoclonal antibodies specific for wild mouse neurotropic retrovirus: detection of comparable levels of virus replication in mouse strains susceptible and resistant to paralytic disease. J Virol. 1985 Dec;56(3):1018–1022. doi: 10.1128/jvi.56.3.1018-1022.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oliff A., Collins L., Mirenda C. Molecular cloning of Friend mink cell focus-inducing virus: identification of mink cell focus-inducing virus-like messages in normal and transformed cells. J Virol. 1983 Nov;48(2):542–546. doi: 10.1128/jvi.48.2.542-546.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Portis J. L., Czub S., Robertson S., McAtee F., Chesebro B. Characterization of a neurologic disease induced by a polytropic murine retrovirus: evidence for differential targeting of ecotropic and polytropic viruses in the brain. J Virol. 1995 Dec;69(12):8070–8075. doi: 10.1128/jvi.69.12.8070-8075.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Power C., McArthur J. C., Johnson R. T., Griffin D. E., Glass J. D., Perryman S., Chesebro B. Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences. J Virol. 1994 Jul;68(7):4643–4649. doi: 10.1128/jvi.68.7.4643-4649.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Prasad G., Stoica G., Wong P. K. The role of the thymus in the pathogenesis of hind-limb paralysis induced by ts1, a mutant of Moloney murine leukemia virus-TB. Virology. 1989 Apr;169(2):332–340. doi: 10.1016/0042-6822(89)90158-x. [DOI] [PubMed] [Google Scholar]
- Sharer L. R. Pathology of HIV-1 infection of the central nervous system. A review. J Neuropathol Exp Neurol. 1992 Jan;51(1):3–11. doi: 10.1097/00005072-199201000-00002. [DOI] [PubMed] [Google Scholar]
- Stephens E. B., Liu Z. Q., Zhu G. W., Adany I., Joag S. V., Foresman L., Berman N. E., Narayan O. Lymphocyte-tropic simian immunodeficiency virus causes persistent infection in the brains of rhesus monkeys. Virology. 1995 Nov 10;213(2):600–614. doi: 10.1006/viro.1995.0032. [DOI] [PubMed] [Google Scholar]
- 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]
- Szurek P. F., Yuen P. H., Jerzy R., Wong P. K. Identification of point mutations in the envelope gene of Moloney murine leukemia virus TB temperature-sensitive paralytogenic mutant ts1: molecular determinants for neurovirulence. J Virol. 1988 Jan;62(1):357–360. doi: 10.1128/jvi.62.1.357-360.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wong P. K., Knupp C., Yuen P. H., Soong M. M., Zachary J. F., Tompkins W. A. ts1, a Paralytogenic mutant of Moloney murine leukemia virus TB, has an enhanced ability to replicate in the central nervous system and primary nerve cell culture. J Virol. 1985 Sep;55(3):760–767. doi: 10.1128/jvi.55.3.760-767.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yuen P. H., Malehorn D., Knupp C., Wong P. K. A 1.6-kilobase-pair fragment in the genome of the ts1 mutant of Moloney murine leukemia virus TB that is associated with temperature sensitivity, nonprocessing of Pr80env, and paralytogenesis. J Virol. 1985 May;54(2):364–373. doi: 10.1128/jvi.54.2.364-373.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yuen P. H., Tzeng E., Knupp C., Wong P. K. The neurovirulent determinants of ts1, a paralytogenic mutant of Moloney murine leukemia virus TB, are localized in at least two functionally distinct regions of the genome. J Virol. 1986 Jul;59(1):59–65. doi: 10.1128/jvi.59.1.59-65.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]