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Journal of Virology, February 2008, p. 1838-1850, Vol. 82, No. 4
0022-538X/08/$08.00+0     doi:10.1128/JVI.02119-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Activation of p90 Ribosomal S6 Kinase by ORF45 of Kaposi's Sarcoma-Associated Herpesvirus and Its Role in Viral Lytic Replication{triangledown}

Ersheng Kuang,1 Qiyi Tang,2,{dagger} Gerd G. Maul,2 and Fanxiu Zhu1*

Department of Biological Science, Florida State University, Tallahassee, Florida 32306-4370,1 The Wistar Institute, Philadelphia, Pennsylvania 191042

Received 25 September 2007/ Accepted 26 November 2007

The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway is essential for infection by a variety of viruses. The p90 ribosomal S6 kinases (RSKs) are direct substrates of ERK and functional mediators of ERK MAPK signaling, but their roles in viral infection have never been examined. We demonstrate that ORF45 of Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with RSK1 and RSK2 and strongly stimulates their kinase activities. The activation of RSK by ORF45 is correlated with ERK activation but does not require MEK. We further demonstrate that RSK1/RSK2 is activated during KSHV primary infection and reactivation from latency; a subset of RSK1/RSK2 is present in the viral replication compartment in the nucleus. Depletion of RSK1/RSK2 by small interfering RNA or the specific inhibitor BI-D1870 suppresses KSHV lytic gene expression and progeny virion production, suggesting an essential role of RSK1/RSK2 in KSHV lytic replication.


* Corresponding author. Mailing address: Department of Biological Science, Florida State University, 89 Chieftan Way, Tallahassee, FL 32306-4370. Phone: (850) 644-6273. Fax: (850) 644-0481. E-mail: fzhu{at}bio.fsu.edu

{triangledown} Published ahead of print on 5 December 2007.

{dagger} Present address: Department of Microbiology/AIDS program, Ponce School of Medicine, 395 Zona Industrial Reparadara-2, Ponce, PR 00716-2348.


Journal of Virology, February 2008, p. 1838-1850, Vol. 82, No. 4
0022-538X/08/$08.00+0     doi:10.1128/JVI.02119-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Kuang, E., Wu, F., Zhu, F. (2009). Mechanism of Sustained Activation of Ribosomal S6 Kinase (RSK) and ERK by Kaposi Sarcoma-associated Herpesvirus ORF45: MULTIPROTEIN COMPLEXES RETAIN ACTIVE PHOSPHORYLATED ERK AND RSK AND PROTECT THEM FROM DEPHOSPHORYLATION. J. Biol. Chem. 284: 13958-13968 [Abstract] [Full Text]  
  • Li, X., Zhu, F. (2009). Identification of the Nuclear Export and Adjacent Nuclear Localization Signals for ORF45 of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 83: 2531-2539 [Abstract] [Full Text]  
  • Kakugawa, S., Shimojima, M., Goto, H., Horimoto, T., Oshimori, N., Neumann, G., Yamamoto, T., Kawaoka, Y. (2009). Mitogen-Activated Protein Kinase-Activated Kinase RSK2 Plays a Role in Innate Immune Responses to Influenza Virus Infection. J. Virol. 83: 2510-2517 [Abstract] [Full Text]