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. 1980 Oct 1;152(4):853–868. doi: 10.1084/jem.152.4.853

Molecular basis of reovirus virulence. Role of the M2 gene

PMCID: PMC2185979  PMID: 7420022

Abstract

The mammalian reoviruses (serotype 1, strain Lang and serotype 3, strain Dearing) differ in their sensitivity to digestion by chymotrypsin. We have found that the M2 double-stranded RNA (dsRNA) genome segment (encoding the micro1C outer capsid polypeptide) is responsible for this property. In addition to determining response to protease treatement in vitro, we have found that the M2 genome segment also determines the ability of these two viruses successfully to initiate local and systemic infection in newborn mice after peroral inoculation. Thus the M2 dsRNA segment defines a new virulence gene of the mammalian reoviruses.

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Selected References

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  1. Babiss L. E., Luftig R. B., Weatherbee J. A., Weihing R. R., Ray U. R., Fields B. N. Reovirus serotypes 1 and 3 differ in their in vitro association with microtubules. J Virol. 1979 Jun;30(3):863–874. doi: 10.1128/jvi.30.3.863-874.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Borsa J., Long D. G., Sargent M. D., Copps T. P., Chapman J. D. Reovirus transcriptase activation in vitro: involvement of an endogenous uncoating activity in the second stage of the process. Intervirology. 1974;4(3):171–188. doi: 10.1159/000149856. [DOI] [PubMed] [Google Scholar]
  3. Borsa J., Sargent M. D., Copps T. P., Long D. G., Chapman J. D. Specific monovalent cation effects on modification of reovirus infectivity by chymotrypsin digestion in vitro. J Virol. 1973 Jun;11(6):1017–1019. doi: 10.1128/jvi.11.6.1017-1019.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Borsa J., Sargent M. D., Long D. G., Chapman J. D. Extraordinary effects of specific monovalent cations on activation of reovirus transcriptase by chymotrypsin in vitro. J Virol. 1973 Feb;11(2):207–217. doi: 10.1128/jvi.11.2.207-217.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cross R. K., Fields B. N. Temperature-sensitive mutants of reovirus type 3: evidence for aberrant mu 1 and mu 2 polypeptide species. J Virol. 1976 Jul;19(1):174–179. doi: 10.1128/jvi.19.1.174-179.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DRAPANAS T., SHIM W. K. Pancreatic secretion in the experimental dumping syndrome. Ann Surg. 1961 Dec;154:934–938. [PMC free article] [PubMed] [Google Scholar]
  7. Gonatas N. K., Margolis G., Kilham L. Reovirus type 3 encephalitis: observations of virus-cell interactions in neural tissues. II. Electron microscopic studies. Lab Invest. 1971 Feb;24(2):101–109. [PubMed] [Google Scholar]
  8. HUMMEL B. C. A modified spectrophotometric determination of chymotrypsin, trypsin, and thrombin. Can J Biochem Physiol. 1959 Dec;37:1393–1399. [PubMed] [Google Scholar]
  9. Ito Y., Joklik W. K. Temperature-sensitive mutants of reovirus. 3. Evidence that mutants of group D ("RNA-negative") are structural polypeptide mutants. Virology. 1972 Oct;50(1):282–286. doi: 10.1016/0042-6822(72)90373-x. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  12. LUNDH G. The mechanism of postgastrectomy malabsorption. Gastroenterology. 1962 May;42:637–640. [PubMed] [Google Scholar]
  13. Margolis G., Kilham L. Hydrocephalus in hamsters, ferrets, rats, and mice following inoculations with reovirus type I. II. Pathologic studies. Lab Invest. 1969 Sep;21(3):189–198. [PubMed] [Google Scholar]
  14. McClain M. E., Spendlove R. S., Lennette E. H. Infectivity assay of Reoviruses: comparison of immunofluorescent cell count and plaque methods. J Immunol. 1967 Jun;98(6):1301–1308. [PubMed] [Google Scholar]
  15. 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]
  16. Mustoe T. A., Ramig R. F., Sharpe A. H., Fields B. N. A genetic map of reovirus. III. Assignment of the double-stranded RNA-positive mutant groups A, B, and G to genome segments. Virology. 1978 Apr;85(2):545–556. doi: 10.1016/0042-6822(78)90460-9. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Peters T. J. The hydrolysis of glycine oligopeptides by guinea-pig intestinal mucosa and by isolated brush borders. Clin Sci Mol Med. 1973 Dec;45(6):803–816. doi: 10.1042/cs0450803. [DOI] [PubMed] [Google Scholar]
  19. ROSEN L., ABINANTI F. R. Natural and experimental infection of catle with human types of reoviruses. Am J Hyg. 1960 Mar;71:250–257. doi: 10.1093/oxfordjournals.aje.a120108. [DOI] [PubMed] [Google Scholar]
  20. ROSEN L. Serologic grouping of reoviruses by hemagglutination-inhibition. Am J Hyg. 1960 Mar;71:242–249. doi: 10.1093/oxfordjournals.aje.a120107. [DOI] [PubMed] [Google Scholar]
  21. Raine C. S., Fields B. N. Reovirus type 3 encephalitis--a virologic and ultrastructural study. J Neuropathol Exp Neurol. 1973 Jan;32(1):19–33. doi: 10.1097/00005072-197301000-00002. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Ramig R. F., Fields B. N. Revertants of temperature-sensitive mutants of reovirus: evidence for frequent extragenic suppression. Virology. 1979 Jan 15;92(1):155–167. doi: 10.1016/0042-6822(79)90221-6. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Robberecht P., Deschodt-Lanckman M., Camus J., Bruylands J., Christophe J. Rat pancreatic hydrolases from birth to weaning and dietary adaptation after weaning. Am J Physiol. 1971 Jul;221(1):376–381. doi: 10.1152/ajplegacy.1971.221.1.376. [DOI] [PubMed] [Google Scholar]
  26. SPENDLOVE R. S., SCHAFFER F. L. ENZYMATIC ENHANCEMENT OF INFECTIVITY OF REOVIRUS. J Bacteriol. 1965 Mar;89:597–602. doi: 10.1128/jb.89.3.597-602.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Samloff I. M. Pepsinogens, pepsins, and pepsin inhibitors. Gastroenterology. 1971 Apr;60(4):586–604. [PubMed] [Google Scholar]
  28. Schreiber D. S., Trier J. S., Blacklow N. R. Recent advances in viral gastroenteritis. Gastroenterology. 1977 Jul;73(1):174–183. doi: 10.1016/S0016-5085(19)32293-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shatkin A. J., LaFiandra A. J. Transcription by infectious subviral particles of reovirus. J Virol. 1972 Oct;10(4):698–706. doi: 10.1128/jvi.10.4.698-706.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Smith R. E., Zweerink H. J., Joklik W. K. Polypeptide components of virions, top component and cores of reovirus type 3. Virology. 1969 Dec;39(4):791–810. doi: 10.1016/0042-6822(69)90017-8. [DOI] [PubMed] [Google Scholar]
  31. Spendlove R. S., McClain M. E., Lennette E. H. Enhancement of reovirus infectivity by extracellular removal or alteration of the virus capsid by proteolytic enzymes. J Gen Virol. 1970 Aug;8(2):83–94. doi: 10.1099/0022-1317-8-2-83. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Weiner H. L., Fields B. N. Neutralization of reovirus: the gene responsible for the neutralization antigen. J Exp Med. 1977 Nov 1;146(5):1305–1310. doi: 10.1084/jem.146.5.1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Weiner H. L., Ramig R. F., Mustoe T. A., Fields B. N. Identification of the gene coding for the hemagglutinin of reovirus. Virology. 1978 May 15;86(2):581–584. doi: 10.1016/0042-6822(78)90099-5. [DOI] [PubMed] [Google Scholar]

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