Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Feb;79(4):1298–1302. doi: 10.1073/pnas.79.4.1298

Molecular basis of reovirus neurovirulence: role of the M2 gene in avirulence.

D B Hrdy, D H Rubin, B N Fields
PMCID: PMC345950  PMID: 6951176

Abstract

A number of field isolates of reovirus 3 were examined to determine their relative neurovirulence after intracerebral inoculation. One isolate was found that had decreased neurovirulence. This "avirulent" strain showed the typical type 3 neural tropism but grew significantly less well in brain tissue than T3 (Dearing) and the other type 3 reoviruses. The avirulent virus was not temperature-sensitive, and its yield in mouse L cells in vitro was similar to that of the laboratory strains. To determine the reason that this clone was avirulent, we isolated a series of reassortant progeny clones from crosses between the avirulent strain and T1 (Lang) and T3 (Dearing). Using these reassortants, we showed that avirulence was a property of the M 2 gene segment. The M2 segment was also responsible for conferring greater sensitivity to chymotryptic digestion on the avirulent strain, compared to more virulent strains. Prior studies have determined that the localization of virus in different cell types in the brain (tropism) is a property of the viral hemagglutinin, the product of the S1 RNA genome segment. Our studies thus indicate that the basis for relative neurovirulence does not reside in the viral hemagglutinin and clearly illustrate the multigenic nature of neurovirulence.

Full text

PDF
1302

Images in this article

1300Image
on p.1300
1301Image
on p.1301

Selected References

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

  1. Bosch F. X., Orlich M., Klenk H. D., Rott R. The structure of the hemagglutinin, a determinant for the pathogenicity of influenza viruses. Virology. 1979 May;95(1):197–207. doi: 10.1016/0042-6822(79)90414-8. [DOI] [PubMed] [Google Scholar]
  2. Fields B. N. Genetic manipulation of reovirus--a model for modification of disease. N Engl J Med. 1972 Nov 16;287(20):1026–1033. doi: 10.1056/NEJM197211162872007. [DOI] [PubMed] [Google Scholar]
  3. Hrdy D. B., Rosen L., Fields B. N. Polymorphism of the migration of double-stranded RNA genome segments of reovirus isolates from humans, cattle, and mice. J Virol. 1979 Jul;31(1):104–111. doi: 10.1128/jvi.31.1.104-111.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Joklik W. K. Studies on the effect of chymotrypsin on reovirions. Virology. 1972 Sep;49(3):700–715. doi: 10.1016/0042-6822(72)90527-2. [DOI] [PubMed] [Google Scholar]
  5. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  6. McCrae M. A., Joklik W. K. The nature of the polypeptide encoded by each of the 10 double-stranded RNA segments of reovirus type 3. Virology. 1978 Sep;89(2):578–593. doi: 10.1016/0042-6822(78)90199-x. [DOI] [PubMed] [Google Scholar]
  7. Mustoe T. A., Ramig R. F., Sharpe A. H., Fields B. N. Genetics of reovirus: identification of the ds RNA segments encoding the polypeptides of the mu and sigma size classes. Virology. 1978 Sep;89(2):594–604. doi: 10.1016/0042-6822(78)90200-3. [DOI] [PubMed] [Google Scholar]
  8. Nagai Y., Shimokata K., Yoshida T., Hamaguchi M., Iinuma M., Maeno K., Matsumoto T., Klenk H. D., Rott R. The spread of a pathogenic and an apathogenic strain of Newcastle disease virus in the chick embryo as depending on the protease sensitivity of the virus glycoproteins. J Gen Virol. 1979 Nov;45(2):263–272. doi: 10.1099/0022-1317-45-2-263. [DOI] [PubMed] [Google Scholar]
  9. Ramig R. F., Cross R. K., Fields B. N. Genome RNAs and polypeptides of reovirus serotypes 1, 2, and 3. J Virol. 1977 Jun;22(3):726–733. doi: 10.1128/jvi.22.3.726-733.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ramig R. F., Mustoe T. A., Sharpe A. H., Fields B. N. A genetic map of reovirus. II. Assignment of the double-stranded RNA-negative mutant groups C, D, and E to genome segments. Virology. 1978 Apr;85(2):531–534. doi: 10.1016/0042-6822(78)90459-2. [DOI] [PubMed] [Google Scholar]
  11. Rozhon E. J., Gensemer P., Shope R. E., Bishop D. H. Attenuation of virulence of a bunyavirus involving an L RNA defect and isolation of LAC/SSH/LAC and LAC/SSH/SSH reassortants. Virology. 1981 May;111(1):125–138. doi: 10.1016/0042-6822(81)90659-0. [DOI] [PubMed] [Google Scholar]
  12. Rubin D. H., Fields B. N. Molecular basis of reovirus virulence. Role of the M2 gene. J Exp Med. 1980 Oct 1;152(4):853–868. doi: 10.1084/jem.152.4.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Scheid A., Choppin P. W. Protease activation mutants of sendai virus. Activation of biological properties by specific proteases. Virology. 1976 Jan;69(1):265–277. doi: 10.1016/0042-6822(76)90213-0. [DOI] [PubMed] [Google Scholar]
  14. Scholtissek C., Vallbracht A., Flehmig B., Rott R. Correlation of pathogenicity and gene constellation of influenza A viruses. II. Highly neurovirulent recombinants derived from non-neurovirulent or weakly neurovirulent parent virus strains. Virology. 1979 Jun;95(2):492–500. doi: 10.1016/0042-6822(79)90503-8. [DOI] [PubMed] [Google Scholar]
  15. Sharpe A. H., Ramig R. F., Mustoe T. A., Fields B. N. A genetic map of reovirus. 1. Correlation of genome RNAs between serotypes 1, 2, and 3. Virology. 1978 Jan;84(1):63–74. doi: 10.1016/0042-6822(78)90218-0. [DOI] [PubMed] [Google Scholar]
  16. Weiner H. L., Ault K. A., Fields B. N. Interaction of reovirus with cell surface receptors. I. Murine and human lymphocytes have a receptor for the hemagglutinin of reovirus type 3. J Immunol. 1980 May;124(5):2143–2148. [PubMed] [Google Scholar]
  17. Weiner H. L., Drayna D., Averill D. R., Jr, Fields B. N. Molecular basis of reovirus virulence: role of the S1 gene. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5744–5748. doi: 10.1073/pnas.74.12.5744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Weiner H. L., Powers M. L., Fields B. N. Absolute linkage of virulence and central nervous system cell tropism of reoviruses to viral hemagglutinin. J Infect Dis. 1980 May;141(5):609–616. doi: 10.1093/infdis/141.5.609. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES