This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.01917-06v1 81/3/1339    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Naito, T. Articles by Nagata, K. Search for Related Content PubMed PubMed Citation Articles by Naito, T. Articles by Nagata, K.

 Previous Article  |  Next Article 

Journal of Virology, February 2007, p. 1339-1349, Vol. 81, No. 3
0022-538X/07/$08.00+0     doi:10.1128/JVI.01917-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Involvement of Hsp90 in Assembly and Nuclear Import of Influenza Virus RNA Polymerase Subunits

Department of Infection Biology, Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan,¹ Department of Infection Control and Immunology, Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan²

Received 2 September 2006/ Accepted 10 November 2006

Transcription and replication of the influenza virus RNA genome occur in the nuclei of infected cells through the viral RNA-dependent RNA polymerase consisting of PB1, PB2, and PA. We previously identified a host factor designated RAF-1 (RNA polymerase activating factor 1) that stimulates viral RNA synthesis. RAF-1 is found to be identical to Hsp90. Here, we examined the intracellular localization of Hsp90 and viral RNA polymerase subunits and their molecular interaction. Hsp90 was found to interact with PB2 and PB1, and it was relocalized to the nucleus upon viral infection. We found that the nuclear transport of Hsp90 occurs in cells expressing PB2 alone. The nuclear transport of Hsp90 was in parallel with that of the viral RNA polymerase binary complexes, either PB1 and PB2 or PB1 and PA, as well as with that of PB2 alone. Hsp90 also interacted with the binary RNA polymerase complex PB1-PB2, and it was dissociated from the PB1-PB2 complex upon its association with PA. Furthermore, Hsp90 could form a stable PB1-PB2-Hsp90 complex prior to the formation of a ternary polymerase complex by the assembly of PA in the infected cells. These results suggest that Hsp90 is involved in the assembly and nuclear transport of viral RNA polymerase subunits, possibly as a molecular chaperone for the polymerase subunits prior to the formation of a mature ternary polymerase complex.

Published ahead of print on 22 November 2006.

This article has been cited by other articles:

• Taguwa, S., Okamoto, T., Abe, T., Mori, Y., Suzuki, T., Moriishi, K., Matsuura, Y. (2008). Human Butyrate-Induced Transcript 1 Interacts with Hepatitis C Virus NS5A and Regulates Viral Replication. J. Virol. 82: 2631-2641 [Abstract] [Full Text]  
• Jorba, N., Area, E., Ortin, J. (2008). Oligomerization of the influenza virus polymerase complex in vivo. J. Gen. Virol. 89: 520-524 [Abstract] [Full Text]  
• Naito, T., Kiyasu, Y., Sugiyama, K., Kimura, A., Nakano, R., Matsukage, A., Nagata, K. (2007). An influenza virus replicon system in yeast identified Tat-SF1 as a stimulatory host factor for viral RNA synthesis. Proc. Natl. Acad. Sci. USA 104: 18235-18240 [Abstract] [Full Text]  
• Castorena, K. M., Weeks, S. A., Stapleford, K. A., Cadwallader, A. M., Miller, D. J. (2007). A Functional Heat Shock Protein 90 Chaperone Is Essential for Efficient Flock House Virus RNA Polymerase Synthesis in Drosophila Cells. J. Virol. 81: 8412-8420 [Abstract] [Full Text]