PKA Inhibitor KT5720, Suppressed Cytoskeletal Components Effect by Vesicular Stomatitis Virus, but did not Affect the Viral Replication

  • Kim, Young-Sook (Department of Oriental Medical Food and Nutrition, Asia University)
  • 발행 : 2007.10.30

초록

The antiviral mechanism of KT5720 is known to inhibit the cAMP-dependent protein kinase (PKA), on the VSV infection in BHK-21 cell cultures. The virus inducted CPE (cell rounding) was almost completely suppressed by KT5720 at 5 uM. The inhibitor, however, did not affect the replication of the virus and the synthesis of viral macromolecules. Immunological studies showed the viral matrix (M) protein displayed intimate association with the cytoskeletal components and probably the cell rounding. KT5720, did not block the cytoskeletal disruption, while the cell rounding was suppressed. These observations suggest that the interaction between the viral M protein and the cytoskeletal components may not be enough to cause the morphological change of the cell. And, the KT5720-sensitive function may be involved in developing the VSV-induced CPE, but not essential for the virus replications.

키워드

참고문헌

  1. 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
  2. Kase, H., Iwahashi, K., Nakanishi, S., Matsuda, Y., Yamada, K., Takahashi, M., Murakata, C., Sato, A., and M. Kaneko (1987), K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases, Biochem. Biophys. Res. Commun. 142, 436-440 https://doi.org/10.1016/0006-291X(87)90293-2
  3. Nakanishi, S., Yamada, K., Kase, H., Nakamura, S., and Y. Nonomura (1988), K-252a, a novel microbial product, inhibits smooth muscle myosin light chain kinase, J. Biol. Chem. 263, 6215-6219
  4. Nakanishi S., Yamada K., Iwahashi K., Kuroda K., and H. Kase (1990), KT5926, a potent and selective inhibitor of myosin. light chain kinase, Mol. Pharmacal. 37, 482-488
  5. 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
  6. Simon, K. O., Whiitaker-Dowling, P. A, Youngner, J. S., 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
  7. Kim, Y. S (2007), A Protein Kinase-A Inhibitor, KT5720, Suppressed Cytopathic Effect Caused by Vesicular Stomatitis Virus, JLS. 17, (in press) https://doi.org/10.5352/JLS.2007.17.10.1361
  8. Blondel, D., Harmison, G. G., and M. Schubert (1990), Role of matrix protein in cytopathogenesis of vesicular stomatitis virus, J. Virol. 64, 1716-1725
  9. Clinton, G. M., Little, S. P., Hagen, F. S., 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
  10. Kaptur, P. E., Rhodes, R. B., and D. S. Lyles (1991), Sequences of the vesicular stomatitis virus matrix protein involved in binding to nucleocapsids, J. Viral. 65, 1057-1065
  11. 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. Viral. 39, 295-299
  12. Chong, L. D. and J. K. Rose (1993), Membrane association of functional vesicular stomatitis virus matrix protein in vivo, J. Vjrol. 67, 407-414
  13. Sun, Y, W., K. Suryanarayana, P. Jusjtice, Robinson, D., and R. R. Wagner (1994), Membrane-binding domains and cytopathogenesis of the matrix protein of vesicular stomatitis virus, J. Viral. 68, 7386-7396
  14. 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
  15. Ono, K., Dubois-Dalcq, M. E., Schubert, M., 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. Viral. 61, 1332-1341
  16. Melki, R., Y. Gardina, and D. Blondel (1994), Interaction between tnbulin 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
  17. Kim, Y. S., Sagara, J., 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
  18. Laemmli, U. K. (1970), Cleavage of Structnral Proteins during the Assembly of the Head of Bacteriophage T4, Nature London 227, 680-685 https://doi.org/10.1038/227680a0
  19. 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 Cytoskelctons, J. Cell Biol. 126, 391-401 https://doi.org/10.1083/jcb.126.2.391
  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. 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
  22. Sagra, J., Tsukita, S., Yonemura, S., Tsukita, S., 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