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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
Identification of Hsp90 as a Stimulatory Host Factor Involved in
Influenza Virus RNA Synthesis*
Fumitaka
Momose §,
Tadasuke
Naito¶,
Keiichi
Yano ,
Seiji
Sugimoto ,
Yuko
Morikawa , and
Kyosuke
Nagata§¶**
From the 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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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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