Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

A Protein Kinase-A Inhibitor, KT5720, Suppressed Cytopathic Effect Caused by Vesicular Stomatitis Virus

Protein Kinase Inhibitor, KT5720의 VSV에 의한 세포변성 억제 연구

  • Kim, Young-Sook (Department of Oriental Medical Food and Nutrition, Asia University)
  • 김영숙 (아시아대학교 한방식품영양학과)
  • Published : 2007.10.30
Download PDF
⟨ Previous Next ⟩

Abstract

I investigated the effect of KT5720, an inhibitor of protein kinase A, on the vesicular stomatitis virus (VSV) infection in BHK-21cell cultures. The virus inducted cytopathic effect (CPE) was almost completely suppressed by KT5720 at 5uM. The inhibitor, however, did not affect replication of the virus nor the synthesis of viral macromolecules. KT5720, did not block the cytoskeletal disruption, while the cell rounding was suppressed. And, the KT5720-sensitive function may be involved in developing the VSV-induced CPE, but not essential for the virus replications.

Nocardiopis sp. 유래의 protein kinase 저해제인 KT5720, KT5926을 사용하여 Vesicular Stomatitis Virus (VSV) 증식에 미치는 세포변성의 억제를 지표로서 연구하였다. 그 결과 CAMP의존 kinase를 저해하는 KT5720, mysion light chain kinase (MLCK)를 저해하는 KT5926이 VSV에 의한 세포변성을 억제시켰다. Protein kinase inhibitor KT5720은 VSV의 증식에 영향을 미치지는 않지만, 세포변성과정은 억제하는 것으로 나타났다. Virus RNA 및 단백질 합성에서 PKA KT5720이 영향을 미치지 않는 것은 virus 증식에 영향이 없는 것으로 나타난다. Virus 증식과정에서 성질이 다른 protein kinase가 관여하는데, 이것은 negative strand virus에 대한 항virus 제 개발에 중요한 역할을 한다고 생각한다.

Keywords

References

  1. Black, B. L. and D. Lyles. 1992. Vesicular stomatitis virus matrix protein inhibits host cell-directed transcription of target genes in vivo. J. Virol. 66, 4058-4064.
  2. Blondel, D., G. G. Harmison and M. Schubert. 1990. Role of matrix protein in cytopathogenesis of vesicular stomatitis virus. J. Virol. 64, 1716-1725.
  3. Carroll, A. R. and R. R. Wagner. 1979. Role of the membrane (M) protein in endogenous inhibition of in vitro transcription by vesicular stomatitis virus. J. Virol. 29, 134-142.
  4. Clinton, G. M., S. P. Little, F. S. Hagen and A. S. Huang. 1978. The matrix (M) protein of vesicular stomatitis virus regulates transcription. Cell 15, 1455-1462. https://doi.org/10.1016/0092-8674(78)90069-7
  5. Chong, L. D. and J. K. Rose. 1993. Membrane association of functional vesicular stomatitis virus matrix protein in vivo. J. Virol. 67, 407-414.
  6. Grinnell, B. W. and R. R. Wagner. 1983. Comparative inhibition of cellular transcription by vesicular stomatitis virus serotypes New Jersey and Indiana: role of each viral leader RNA. J. Virol. 48, 88-101.
  7. Gross-Bellard, M., P. Oudet and P. Chambon. 1973. Isolation of High-Molecular-Weight DNA from Mammalian Cells. J. Biochem. 36, 32-38.
  8. Honda, Y., A. Kawai and J. Matsumoto. 1984. Comparative Studies of Rabies and Sindbis Virus Replication in Human Neuroblastoma (SYM-I) Cells that Can Produce Interferon J. Gen. Virol. 65, 1645-1653. https://doi.org/10.1099/0022-1317-65-10-1645
  9. Kaptur, P. E., R. B. Rhodes and D. S. Lyles. 1991. Sequences of the vesicular stomatitis virus matrix protein involved in binding to nucleocapsids. J. Virol. 65, 1057-1065.
  10. Kawai, A. 1977. Transcriptase Activity Associated with Rabies Virion. J. Virol. 24, 826-835.
  11. Kase, H., K. Iwahashi, S. Nakanisji, Y. Matsuda, K. Yamada, M. Takahashi, C. Murakata, A. Sato and M. Kaneko. 1987. K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases. Biochem. Biophys. Res. Comm. 142, 436-440. https://doi.org/10.1016/0006-291X(87)90293-2
  12. Kim, Y. S. and A. Kawai. 1998. Studies on the AntiviralMechanisms of protein kinase inhibitors K-252a and KT5926 against the replication of Vesicular stomatitis virus. Biol. Pharm. Bull. 21, 498-505. https://doi.org/10.1248/bpb.21.498
  13. Kim, Y. S., J. Sagara and A. Kawai. 1995. Studies on the Antiviral Activity of protein kinase inhibitors against the replication of Vesicular stomatitis virus. Biol. Pharm. Bull. 18, 895-899. https://doi.org/10.1248/bpb.18.895
  14. Kurilla, M. G., H. Piwnica-Worms and J. D. Keene. 1982. Rapid and Transient Localization of the Leader RNA of Vesicular Stomatitis Virus in the Nuclei of Infected Cells. Proc. Natl. Acid. Sci. USA 79, 5240-5244. https://doi.org/10.1073/pnas.79.17.5240
  15. Laemmli, U. K. 1970. Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4. Nature London 227, 680-685. https://doi.org/10.1038/227680a0
  16. Levine, B., Q. Huang, J. T. Isaacs, J. C. Reed, D. E. Griffin and J. M. Hardwick. 1993. Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature 361, 739-742. https://doi.org/10.1038/361739a0
  17. McGowan, J. J., S. U. Emerson and R. R. Wagner. 1982. The plus-strand leader RNA of VSV inhibits DNA-dependent transcription of adenovirus and SV40 genes in a soluble whole-cell extract. Cell 28, 325-333. https://doi.org/10.1016/0092-8674(82)90350-6
  18. Melki, R., Y. Gardina and D. Blondel. 1994. Interaction between tubulin and the viral matrix protein of vesicular stomatitis virus: possible implications in the viral cytopathic effect. Virology 202, 339-347. https://doi.org/10.1006/viro.1994.1350
  19. Morimoto, K., Y. J. Ni and A. Kawai. 1992. Syncytium formation is induced in the murine neuroblastoma cell cultures which produce pathogenic type G proteins of the rabies virus. Virology 189, 203-216. https://doi.org/10.1016/0042-6822(92)90696-M
  20. Naito, S. and S. Matsumoto. 1978. Identification of cellular actin within the rabies virus. Virology 91, 151-163. https://doi.org/10.1016/0042-6822(78)90363-X
  21. Nakanishi, S., K. Yamada, H. Kase, S. Nakamura and Y. Nonomura. K-252a, a novel microbial product, inhibits smooth muscle myosin light chain kinase J. Biol. Chem. 263, 6215-6219.
  22. Nakanishi, S., K. Yamada, K. Iwahashi, K. Kuroda and H. Kase. 1990. KT5926, a Potent and Selective Inhibitor of Myosin Light Chain Kinase. Molec. Phamacol. 37, 482-488.
  23. Newcomb, W. W. and J. C. Brown. 1981. Role of the vesicular stomatitis virus matrix protein in maintaining the viral nucleocapsid in the condensed form found in native virions. J. Virol. 39, 295-299.
  24. Ono, K., M. E. Dubois-Dalcq, M. Schubert and R. A. Lazzarini. 1987. A mutated membrane protein of vesicular stomatitis virus has an abnormal distribution within the infected cell and causes defective budding. J. Virol. 61, 1332-1341.
  25. Rutter, G. and K. Mannweiler. 1977. Alterations of Actin-Containing Structures in BHK21 Cells Infected with Newcastle Disease Virus and Vesicular Stomatitis Virus. J. Gen. Virol. 37, 233-242. https://doi.org/10.1099/0022-1317-37-2-233
  26. Sagara, J. and A. Kawai. 1992. Identification of heat shock protein 70 in the rabies virion. Virology 190, 845-848. https://doi.org/10.1016/0042-6822(92)90923-D
  27. Sagra, J., S. Tsukita, S. Yonemura, S. Tsukita and A. Kawai. 1995. Cellular actin-binding ezrin-radixin-moesin (ERM) family proteins are incorporated into the rabies virions and closely associated with viral envelope proteins in the cell. Virology 206, 485-494. https://doi.org/10.1016/S0042-6822(95)80064-6
  28. Simon, K. O., P. A. Whiitaker-Dowling, J. S. Youngner and C. C. Widnell. 1990. Cited by other Osatomi and Sumiyoshi, Complete Nucleotide Sequence of Dengue Type 3 Virus Genome. Virology 177, 289-305. https://doi.org/10.1016/0042-6822(90)90482-7
  29. Sun, Y. W., K. Suryanarayana, P. Jusjtice, D. Robinson and R. R. Wagner. 1994. Membrane-binding domains and cytopathogenesis of the matrix protein of vesicular stomatitis virus. J. Virol. 68, 7386-7396.
  30. Tsukita, S., K. Oishi, N. Sato, J. Sagara, A. Kawai and S. Tsukita. 1994. ERM Family Members as Molecular Linkers between the Cell Surface Glycoprotdn CD44 and Actin-based Cytoskeletons. J. Cell Biol. 126, 391-401. https://doi.org/10.1083/jcb.126.2.391
  31. Weck, P. K., A. R. Caeeol, D. M. Shattuck and R. R. Wagner. 1976. Use of UV Irradiation to Identify the Genetic Information of Vesicular Stomatitis Virus Responsible for Shutting Off Cellular RNA Synthesis. J. Virol. 30, 746-753.
  32. Willson, T. and J. Lenard. 1981. Interaction of wild-type and mutant M protein of vesicular stomatitis virus with nucleocapsids in vitro. Biochemistry 20, 1349-1354. https://doi.org/10.1021/bi00508a048