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Journal of Virology, October 2008, p. 10102-10110, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.00599-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Sendai Virus C Protein Plays a Role in Restricting PKR Activation by Limiting the Generation of Intracellular Double-Stranded RNA{triangledown}

Kenji Takeuchi,1 Takayuki Komatsu,1 Yoshinori Kitagawa,2 Kiyonao Sada,1 and Bin Gotoh1,2*

Microbiology Section, Department of Pathological Sciences, Faculty of Medical Sciences, University of Fukui, Shimoaizuki 23-3, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan,1 Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan2

Received 18 March 2008/ Accepted 2 August 2008

Sendai virus (SeV) C protein is a multifunctional protein that plays important roles in regulating viral genome replication and transcription, antagonizing the host interferon system, suppressing virus-induced apoptosis, and facilitating virus assembly and budding. We here report a novel role of SeV C protein, the limitation of double-stranded RNA (dsRNA) generation for maintaining the rate of protein synthesis in infected cells. It was found that the intracellular protein synthesis rate was maintained even after wild-type (wt) SeV infection, but markedly suppressed following C-knockout SeV infection. This indicates the requirement of C protein for maintaining protein synthesis after infection. In contrast to wt SeV infection, C-knockout SeV infection caused phosphorylation of both the translation initiation factor eIF2{alpha} and dsRNA-dependent protein kinase (PKR). Phosphorylation of eIF2{alpha} occurred mainly due to the action of PKR, since knockdown of PKR by small interfering RNA limited eIF2{alpha} phosphorylation. C protein, however, could inhibit neither poly(I):poly(C)-activated nor Newcastle disease virus-induced phosphorylation of PKR and eIF2{alpha}, suggesting that C protein does not target common pathways leading to PKR activation. Immunofluorescent staining experiments with a monoclonal antibody specifically recognizing dsRNA revealed generation of a large amount of dsRNA in cells infected with C-knockout SeV but not wt SeV. The dsRNA generation as well as phosphorylation of PKR and eIF2{alpha} induced by C-knockout SeV was markedly suppressed in cells constitutively expressing C protein. Taken together, these results demonstrate that the SeV C protein limits generation of dsRNA, thereby keeping PKR inactive to maintain intracellular protein synthesis.

* Corresponding author. Mailing address: Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan. Phone: 81-77-548-2176. Fax: 81-77-548-2176. E-mail: bing{at}belle.shiga-med.ac.jp

{triangledown} Published ahead of print on 6 August 2008.

Journal of Virology, October 2008, p. 10102-10110, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.00599-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pillet, S., von Messling, V. (2009). Canine Distemper Virus Selectively Inhibits Apoptosis Progression in Infected Immune Cells. J. Virol. 83: 6279-6287 [Abstract] [Full Text]  
  • Toth, A. M., Devaux, P., Cattaneo, R., Samuel, C. E. (2009). Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus. J. Virol. 83: 961-968 [Abstract] [Full Text]  


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