title: Global impact of influenza virus on cellular pathways is mediated by both replication-dependent and -independent events.
abstract: 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.
authors: Department of Microbiology, School of Medicine, University of Washington, Seattle 98195, USA. geiss@u.washington.edu
authors: G K
authors: GK
authors: Geiss
authors: M C
authors: MC
authors: An
authors: R E
authors: RE
authors: Bumgarner
authors: E
authors: E
authors: Hammersmark
authors: D
authors: D
authors: Cunningham
authors: M G
authors: MG
authors: Katze
mesh_terms: D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009975:Orthomyxoviridae / Q000378:metabolism / Q000502:physiology*; D014466:Ultraviolet Rays; D014779:Virus Replication