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Journal of Virology, May 2001, p. 4321-4331, Vol. 75, No. 9
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.9.4321-4331.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Global Impact of Influenza Virus on Cellular
Pathways Is Mediated by both Replication-Dependent and
-Independent Events
Gary K.
Geiss,1,*
Mahru C.
An,2
Roger E.
Bumgarner,1,2
Erick
Hammersmark,1
Dawn
Cunningham,2 and
Michael G.
Katze1,2
Department of Microbiology, School of
Medicine,1 and Washington Regional
Primate Research Center,2 University of
Washington, Seattle 98195
Received 20 November 2000/Accepted 29 January 2001
Influenza virus, the causative agent of the common flu, is a
worldwide health problem with significant economic consequences. Studies of influenza virus biology have revealed elaborate mechanisms by which the virus interacts with its host cell as it inhibits the
synthesis of cellular proteins, evades the innate antiviral response,
and facilitates production of viral RNAs and proteins. With the advent
of DNA array technology it is now possible to obtain a large-scale view
of how viruses alter the environment within the host cell. In this
study, the cellular response to influenza virus infection was examined
by monitoring the steady-state mRNA levels for over 4,600 cellular
genes. Infections with active and inactivated influenza viruses
identified changes in cellular gene expression that were dependent on
or independent of viral replication, respectively. Viral replication
resulted in the downregulation of many cellular mRNAs, and the effect
was enhanced with time postinfection. Interestingly, several genes
involved in protein synthesis, transcriptional regulation, and cytokine
signaling were induced by influenza virus replication, suggesting that
some may play essential or accessory roles in the viral life cycle or
the host cell's stress response. The gene expression pattern induced
by inactivated viruses revealed induction of the cellular metallothionein genes that may represent a protective response to
virus-induced oxidative stress. Genome-scale analyses of virus infections will help us to understand the complexities of virus-host interactions and may lead to the discovery of novel drug targets or
antiviral therapies.
*
Corresponding author. Mailing address: Department of
Microbiology, Box 357242, University of Washington, Seattle, WA 98195. Phone: (206) 732-6155. Fax: (206) 732-6055. E-mail:
geiss{at}u.washington.edu.
Journal of Virology, May 2001, p. 4321-4331, Vol. 75, No. 9
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.9.4321-4331.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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