Journal of Microbiology

The Microbiological Society of Korea (한국미생물학회)
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Reovirus and Tumor Oncolysis

  • Kim, Man-Bok (Department of Biochemistry and Molecular Biology Faculty of Medicine, University of Calgary) ;
  • Chung, Young-Hwa (Department Nanomedical Engineering Pusan National University) ;
  • Johnston, Randal N. (Department of Biochemistry and Molecular Biology Faculty of Medicine, University of Calgary)
  • Published : 2007.06.30
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Abstract

REOviruses (Respiratory Enteric Orphan viruses) are ubiquitous, non-enveloped viruses containing 10 segments of double-stranded RNA (dsRNA) as their genome. They are common isolates of the respiratory and gastrointestinal tract of humans but are not associated with severe disease and are therefore considered relatively benign. An intriguing characteristic of reovirus is its innate oncolytic potential, which is linked to the transformed state of the cell. When immortalized cells are transfected in vitro with activated oncogenes such as Ras, Sos, v-erbB, or c-myc, they became susceptible to reovirus infection and subsequent cellular lysis, indicating that oncogene signaling pathways are exploited by reovirus. This observation has led to the use of the virus in clinical trials as an anti-cancer agent against oncogenic tumors. In addition to the exploitation of oncogene signaling, reovirus may further utilize host immune responses to enhance its antitumor activity in vivo due to its innate interferon induction ability. Reovirus is, however, not entirely benign to immunocompromised animal models. Reovirus causes so-called "black feet syndrome" in immunodeficient mice and can also harm neonatal animals. Because cancer patients often undergo immunosuppression due to heavy chemo/radiation-treatments or advanced tumor progression, this pathogenic response may be a hurdle in virus-based anticancer therapies. However, a genetically attenuated reovirus variant derived from persistent reovirus infection of cells in vitro is able to exert potent anti-tumor activity with significantly reduced viral pathogenesis in immunocompromised animals. Importantly, in this instance the attenuated, reovirus maintains its oncolytic potential while significantly reducing viral pathogenesis in vivo.

Keywords

References

  1. Ahmed, M., S.D. Cramer, and D.S. Lyles. 2004. Sensitivity of prostate tumors to wild type and M protein mutant vesicular stomatitis viruses. Virology 330, 34-49 https://doi.org/10.1016/j.virol.2004.08.039
  2. Ahmed, R., W.M. Canning, R.S. Kauffman, A.H. Sharpe, J.V. Hallum, and B.N. Fields. 1981. Role of the host cell in persistent viral infection: coevolution of L cells and reovoirus during persistent infection. Cell 25, 325-332 https://doi.org/10.1016/0092-8674(81)90050-7
  3. Alain, T., J.F. Wong, S. Urbanski, P. Lee, A.E. Kossakowska, R.N. Johnston, and P.L. Beck. 2007. Reovirus decreases azoxymethane- induced aberrant crypt foci and colon cancer in a rodent model. Cancer Gene Ther. (in press)
  4. Alain, T., M. Kim, R.N. Johnston, S.J. Urbanski, A.E. Kossakowska, P.A.J. Forsyth, and P.W.K. Lee. 2006. The oncolytic effect in vivo of reovirus on tumour cells that have survived reovirus cell killing in vitro. Br. J. Cancer 95, 1020-1027 https://doi.org/10.1038/sj.bjc.6603363
  5. Baer, G.S, D.H. Ebert, C.J. Chung, A.H. Erickson, and T.S. Dermody. 1999. Mutant cells selected during persistent reovirus infection do not express mature cathepsin L and do not support reovirus disassembly. J. Virol. 73, 9532-9543
  6. Baty, C.J. and B. Sherry. 1993. Cytopathogenic effect in cardiac myocytes but not in cardiac fibroblasts is correlated with reovirus- induced acute myocarditis. J. Virol. 67, 6295-6298
  7. Bischoff, J.R., D.H. Kirn, A.Williams, C. Heise, S. Horn, M. Muna, L. Ng, J.A. Nye, A. Sampson-Johannes, A. Fattaey, and F. McCormick. 1996. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274, 373- 376 https://doi.org/10.1126/science.274.5286.373
  8. Bos, J.L. 1989. Ras oncogenes in human cancer: a review. Cancer Res. 49, 4682-4689
  9. Carroll, P.E, M. Okuda, H.F. Horn, P. Biddinger, P.J. Stambrook, L.L. Gleich, Y.Q. Li, P. Tarapore, and K. Fukasawa. 1999. Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression. Oncogene 18, 1935-1944 https://doi.org/10.1038/sj.onc.1202515
  10. Coffey, M.C., J.E. Strong, P.A. Forsyth, and P.W. Lee. 1998. Reovirus therapy of tumors with activated Ras pathway Science 282, 1332-1334 https://doi.org/10.1126/science.282.5392.1332
  11. DeBiasi, R.L., B.A. Robinson, B. Sherry, R. Bouchard, R.D. Brown, M. Rizeq, C. Long, and K.L. Tyler. 2004. Caspase inhibition protects against reovirus-induced myocardial injury in vitro and in vivo. J. Virol. 78, 11040-11050 https://doi.org/10.1128/JVI.78.20.11040-11050.2004
  12. Dermody, T.S. 1998. Molecular mechanisms of persistent infection by reovirus. Curr. Top Microbiol. Immunol. 233(Pt 2), 1-22
  13. Dichter, M.A. and H.L. Weiner. 1984. Infection of neuronal cell cultures with reovirus mimics in vitro patterns of neurotropism. Ann. Neurol. 16, 603-610 https://doi.org/10.1002/ana.410160512
  14. Duncan, M.R., S.M. Stanish, and D.C. Cox. 1978. Differential sensitivity of normal and transformed human cells to reovirus infection. J. Virol. 28, 444-449
  15. Duursma, A.M. and R. Agami. 2003. Ras interference as cancer therapy. Semin. Cancer Biol. 13, 267-273 https://doi.org/10.1016/S1044-579X(03)00040-3
  16. Ebert, D.H, S.A. Kopecky-Bromberg, and T.S. Dermody. 2004. Cathepsin B is inhibited in mutant cells selected during persistent reovirus infection. J. Biol. Chem. 279, 3837-3851 https://doi.org/10.1074/jbc.M310048200
  17. Ebert, O., S. Harbaran, K. Shinozaki, and S.L. Woo. 2005. Systemic therapy of experimental breast cancer metastases by mutant vesicular stomatitis virus in immune-competent mice. Cancer Gene Ther. 12, 350-358 https://doi.org/10.1038/sj.cgt.7700794
  18. Egan, C., M. Kim, and R.N. Johnston. 2003. Increased expression of human c-Myc renders cells sensitive to reovirus oncolysis. AACR Annual General Meeting, Washington, D.C., USA
  19. Haller, B.L, M.L. Barkon, G.P. Vogler, and H.W. Virgin 4th. 1995. Genetic mapping of reovirus virulence and organ tropism in severe combined immunodeficient mice: organ-specific virulence genes. J. Virol. 69, 357-364
  20. Hashiro, G., P.C. Loh, and J.T. Yau. 1977. The preferential cytotoxicity of reovirus for certain transformed cell lines. Arch. Virol. 54, 307-315 https://doi.org/10.1007/BF01314776
  21. Heggie, A.D. and L. Gaddis. 1979. Effects of viral exposure of the two-cell mouse embryo on cleavage and blastocyst formation in vitro. Pediatr. Res. 13, 937-941 https://doi.org/10.1203/00006450-197908000-00013
  22. Heinzerling, L., V. Kunzi, P.A. Oberholzer, T. Kundig, H. Naim, and R. Dummer. 2005. Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells. Blood 106, 2287-2294 https://doi.org/10.1182/blood-2004-11-4558
  23. Heise, C., T. Hermiston, L. Johnson, G. Brooks, A. Sampson- Johannes, A. Williams, L. Hawkins, and D. Kirn. 2000. An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy. Nat. Med. 6, 1134-1139 https://doi.org/10.1038/80474
  24. Jackson, G.G. and R.L. Muldoon. 1973. Viruses causing common respiratory infection in man. IV. Reoviruses and adenoviruses. J. Infect. Dis. 128, 811-833 https://doi.org/10.1093/infdis/128.6.811
  25. Jun, H.S. and J.W. Yoon. 2003. A new look at viruses in type 1 diabetes. Diabetes Metab. Res. Rev. 19, 8-31 https://doi.org/10.1002/dmrr.337
  26. Kim, J.H., Y.S. Lee, H. Kim, J.H. Huang, A.R. Yoon, and C.O. Yun. 2006. Relaxin expression from tumor-targeting adenoviruses and its intratumoral spread, apoptosis induction and efficacy. J. Natl. Cancer Inst. 98, 1482-1493 https://doi.org/10.1093/jnci/djj397
  27. Kim, M. 2005. Mechanisms of resistance to reoviral oncolysis. Ph. D. Thesis. University of Calgary, Alberta, Canada
  28. Kim, M., C. Egan, T. Alain, S.J. Urbanski, P.W.K. Lee, P.A.J. Forsyth, and R.N. Johnston. 2007a. Acquired resistance to reoviral oncolysis in Ras-transformed fibrosarcoma cells. Oncogene 26, 4124-4134 https://doi.org/10.1038/sj.onc.1210189
  29. Kim, M., N. Nieden, S.D. Loken, S.J. Urbanski, P.W.K. Lee, D.E. Rancourt, and R.N. Johnston. 2007b. Safety of attenuated reovirus on the developmental potential of embryonic stem cells. The 4th International Conference on Oncolytic Viruses As Cancer Therapeutics. Scottsdale, AZ, USA
  30. Kim, M., T. Alain, S.J. Urbanski, A.E. Kossakowska, P.W.K. Lee, P.A.J. Forsyth, and R.N. Johnston. 2007c. An attenuated reovirus isolated from persistent reovirus infection exerts viral oncolysis with reduced pathogenicity. The 4th International Conference on Oncolytic Viruses As Cancer Therapeutics. Scottsdale, AZ, USA
  31. Kirn, D. 2001. Oncolytic virotherapy for cancer with the adenovirus dl1520 (Onyx-015): results of phase I and II trials. Expert Opin. Biol. Ther. 1, 525-538 https://doi.org/10.1517/14712598.1.3.525
  32. Loken, S.D., K. Norman, K. Hirasawa, M. Nodwell, W.M. Lester, and D.J. Demetrick. 2004. Morbidity in immunosuppressed (SCID/NOD) mice treated with reovirus (dearing 3) as an anticancer biotherapeutic. Cancer Biol. Ther. 3, 734-73 https://doi.org/10.4161/cbt.3.8.963
  33. Lun, X., W. Yang, T. Alain, Z.Q. Shi, H. Muzik, J.W. Barrett, G. McFadden, J. Bell, M.G. Hamilton, D.L. Senger, and P.A. Forsyth. 2005. Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas. Cancer Res. 65, 9982-9990 https://doi.org/10.1158/0008-5472.CAN-05-1201
  34. Mann, M.A, K.L. Tyler, D.M Knipe, and B.N. Fields. 2002. Type 3 reovirus neuroinvasion after intramuscular inoculation: viral genetic determinants of lethality and spinal cord infection. Virology 303, 213-221 https://doi.org/10.1006/viro.2002.1698
  35. McFadden, G. 2005. Poxvirus tropism. Nat. Rev. Microbiol. 3, 201-213 https://doi.org/10.1038/nrmicro1099
  36. Minuk, G.Y., N. Rascanin, R.W. Paul, P.W. Lee, K. Buchan, and J.K. Kelly. 1987. Reovirus type 3 infection in patients with primary biliary cirrhosis and primary sclerosing cholangitis. J. Hepatol. 5, 8-13 https://doi.org/10.1016/S0168-8278(87)80054-5
  37. Minuk, G.Y., R.W. Paul, and P.W. Lee. 1985. The prevalence of antibodies to reovirus type 3 in adults with idiopathic cholestatic liver disease. J. Med. Virol. 16, 55-60 https://doi.org/10.1002/jmv.1890160108
  38. Morris, S.M. 2002. A role for p53 in the frequency and mechanism of mutation. Mutat. Res. 511, 45-62 https://doi.org/10.1016/S1383-5742(01)00075-8
  39. Nakamura, T. and S.J. Russell. 2004. Oncolytic measles viruses for cancer therapy. Expert Opin. Biol. Ther. 4, 1685-1692 https://doi.org/10.1517/14712598.4.10.1685
  40. Nibert, M.L. and L.A. Schiff. 2001. Reoviruses and their replication. p. 1679-1728, In B.N. Fields, D.M Knipe, and P.M. Howley, (eds.). Fields Virology, Lippincott-Raven Publisher, Philadelphia, USA
  41. Norman, K.L. and P.W. Lee. 2005. Not all viruses are bad guys: the case for reovirus in cancer therapy. Drug Discov. Today 10, 847-855 https://doi.org/10.1016/S1359-6446(05)03483-5
  42. Priscott, P.K. 1983. The growth of reovirus 3 in cultured rat embryos and implications for human reproductive failure. Br. J. Exp. Pathol. 64, 467-473
  43. Richardson, S.C., R.F. Bishop, and A.L. Smith. 1994. Reovirus serotype 3 infection in infants with extrahepatic biliary atresia or neonatal hepatitis. J. Gastroenterol. Hepatol. 9, 264-268 https://doi.org/10.1111/j.1440-1746.1994.tb01721.x
  44. Ring, C.J. Cytolytic viruses as potential anti-cancer agents. 2002. J. Gen. Virol. 83, 491-502 https://doi.org/10.1099/0022-1317-83-3-491
  45. Rosen, L., H.E. Evans, and A. Spickard. 1963. Reovirus infections in human volunteers. Am. J. Epidemiol. 77, 29-37 https://doi.org/10.1093/oxfordjournals.aje.a120293
  46. Roberts, M.S., R.M. Lorence, W.S. Groene, and M.K. Bamat. 2006. Naturally oncolytic viruses. Curr. Opin. Mol. Ther. 8, 314-321
  47. Russell, S.J. 2002. RNA viruses as virotherapy agents. Cancer Gene Ther. 9, 961-966 https://doi.org/10.1038/sj.cgt.7700535
  48. Sabin, A.B. 1959. Reoviruses. A new group of respiratory and enteric viruses formerly classified as ECHO type 10 is described. Science 130, 1387-1389 https://doi.org/10.1126/science.130.3386.1387
  49. Steele, T.A. and C.C Hauser. 2005. The role of interferon-alpha in a successful murine tumor therapy. Exp. Biol. Med. 230, 487-493 https://doi.org/10.1177/153537020523000707
  50. Steele, T.A. and D.C. Cox. 1995. Reovirus type 3 chemoimmunotherapy of murine lymphoma is abrogated by cyclosporine. Cancer Biother. 10, 307-315 https://doi.org/10.1089/cbr.1995.10.307
  51. Stoeckel, J. and J.G. Hay. 2006. Drug evaluation: Reolysin-wild-type reovirus as a cancer therapeutic. Curr. Opin. Mol. Ther. 8, 249-260
  52. Stojdl, D.F., B. Lichty, S. Knowles, R. Marius, H. Atkins, N. Sonenberg, and J.C. Bell. 2000. Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat. Med. 6, 821-825 https://doi.org/10.1038/77558
  53. Stojdl, D.F., B.D. Lichty, B.R. TenOever, J.M. Paterson, A.T. Power, S. Knowles, R. Marius, J. Reynerd, L. Poliquin, H. Atkins, E.G. Brown, R.K. Durbin, J.E. Durbin, J. Hiscott, and J.C. Bell. 2003. VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents. Cancer Cell. 4, 263-275 https://doi.org/10.1016/S1535-6108(03)00241-1
  54. Strong, J.E., M.C. Coffey, D. Tang, P. Sabinin, and P.W. Lee. 1998. The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus. EMBO J. 17, 3351-3362 https://doi.org/10.1093/emboj/17.12.3351
  55. Strong, J.E. and P.W. Lee. 1996. The v-erbB oncogene confers enhanced cellular susceptibility to reovirus infection. J. Virol. 70, 612-616
  56. Takai, Y., T. Sasaki, and T. Matozaki. 2001. Small GTP-binding proteins. Physiol. Rev. 81, 153-208 https://doi.org/10.1152/physrev.2001.81.1.153
  57. Terheggen, F., E. Benedikz, P.H. Frissen, and K. Brinkman. 2003. Myocarditis associated with reovirus infection. Eur. J. Clin. Microbiol. Infect. Dis. 22, 197-198
  58. Thorne, S.H., D.L. Bartlett, and D.H. Kirn. 2005. The use of oncolytic Vaccinia viruses in the treatment of cancer: a new role for an old ally? Curr. Gene Ther. 5, 429-443 https://doi.org/10.2174/1566523054546215
  59. Tyler, K.L. 2001. Mammalian reoviruses, p. 1729-1745. In B.N. Fields, D.M. Knipe, and P.M. Howley (eds), Fields Virology, Lippincott-Raven, Philadelphia, USA
  60. Wang, G., J.W. Barrett, M. Stanford, S.J. Werden, J.B. Johnston, X. Gao, M. Sun, J.Q. Cheng, and G. McFadden. 2006. Infection of human cancer cells with myxoma virus requires Akt activation via interaction with a viral ankyrin-repeat host range factor. Proc. Natl. Acad. Sci. USA 103, 4640-4645
  61. Weiner, H.L., D. Drayna, D.R. Averill, Jr., and B.N. Fields. 1977. Molecular basis of reovirus virulence: role of the S1 gene. Proc. Natl. Acad. Sci. USA 74, 5744-5748
  62. Weiner, H.L., M.L. Powers, and B.N. Fields. 1980. Absolute linkage of virulence and central nervous system cell tropism of reoviruses to viral hemagglutinin. J. Infect. Dis. 141, 609-616 https://doi.org/10.1093/infdis/141.5.609