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Journal of Virology, June 2009, p. 5773-5783, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00103-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Regulation of the Catalytic Activity of Herpes Simplex Virus 1 Protein Kinase Us3 by Autophosphorylation and Its Role in Pathogenesis{triangledown}

Ken Sagou,1,3 Takahiko Imai,1 Hiroshi Sagara,2 Masashi Uema,1 and Yasushi Kawaguchi1*

Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases,1 Department of Basic Medical Science, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639,2 Nippon Institute for Biological Science, Ome, Tokyo 198-0024, Japan3

Received 16 January 2009/ Accepted 9 March 2009

Us3 is a serine/threonine protein kinase encoded by herpes simplex virus 1 (HSV-1). We recently identified serine at Us3 position 147 (Ser-147) as a physiological phosphorylation site of Us3 (A. Kato, M. Tanaka, M. Yamamoto, R. Asai, T. Sata, Y. Nishiyama, and Y. Kawaguchi, J. Virol. 82:6172-6189, 2008). In the present study, we investigated the effects of phosphorylation of Us3 Ser-147 on regulation of Us3 catalytic activity in infected cells and on HSV-1 pathogenesis. Our results were as follows. (i) Only a small fraction of Us3 purified from infected cells was phosphorylated at Ser-147. (ii) Us3 phosphorylated at Ser-147 purified from infected cells had significantly higher kinase activity than Us3 not phosphorylated at Ser-147. (iii) Phosphorylation of Us3 Ser-147 in infected cells was dependent on Us3 kinase activity. (iv) Replacement of Us3 Ser-147 by alanine significantly reduced viral replication in the mouse cornea and the development of herpes stromal keratitis and periocular skin disease in mice. These results indicated that Us3 catalytic activity is tightly regulated by autophosphorylation of Ser-147 in infected cells and that regulation of Us3 activity by autophosphorylation appeared to play a critical role in viral replication in vivo and in HSV-1 pathogenesis.

* Corresponding author. Mailing address: Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-6409-2070. Fax: 81-3-6409-2072. E-mail: ykawagu{at}ims.u-tokyo.ac.jp

{triangledown} Published ahead of print on 18 March 2009.

Journal of Virology, June 2009, p. 5773-5783, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00103-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Morimoto, T., Arii, J., Tanaka, M., Sata, T., Akashi, H., Yamada, M., Nishiyama, Y., Uema, M., Kawaguchi, Y. (2009). Differences in the Regulatory and Functional Effects of the Us3 Protein Kinase Activities of Herpes Simplex Virus 1 and 2. J. Virol. 83: 11624-11634 [Abstract] [Full Text]  


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