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Originally published In Press as doi:10.1074/jbc.M206822200 on September 10, 2002

J. Biol. Chem., Vol. 277, Issue 47, 45306-45314, November 22, 2002
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Identification of Hsp90 as a Stimulatory Host Factor Involved in Influenza Virus RNA Synthesis*

Fumitaka MomoseDagger §, Tadasuke Naito, Keiichi Yano||, Seiji Sugimoto||, Yuko MorikawaDagger , and Kyosuke Nagata§**

From the Dagger  Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, the  Department of Infection Biology, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, the || Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 3-6-6 Asahi-machi, Machida-shi, Tokyo 194-8533, Japan, and the § Tokyo Institute of Technology, Nagatsuta, Yokohama 226-8501, Japan

Efficient transcription and replication of the influenza virus genome are dependent upon host-derived factors. Using an in vitro RNA synthesis system, we have purified and identified Hsp90 as one of the host factors that stimulate viral RNA polymerase activity. Hsp90 interacted with the PB2 subunit of the viral RNA polymerase through the amino-terminal chaperone domain and the middle region containing a highly acidic domain. The acidic middle region was also responsible for its stimulatory activity. We found that a portion of Hsp90 is re-localized to the cell nucleus after viral infection. A PB2 fragment containing a Hsp90 binding domain inhibited viral gene expression in a dominant-negative manner. These results suggest that Hsp90 is a host factor for the influenza virus RNA polymerase.


* This work was supported in part by a grant-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and by a grant for the Bioarchitect Research Program from RIKEN (Institute of Physical and Chemical Research, Japan) (to K. N.), and by a research fellowship from the Japan Society for the Promotion of Science for Young Scientists (to F. M.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

** To whom correspondence should be addressed. Current address: Dept. of Infection Biology, Inst. of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan. Tel.: 81-298-53-3233; Fax: 81-298-53-3134; E-mail: knagata@md.tsukuba.ac.jp.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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