Global impact of influenza virus on cellular pathways is mediated by both replication-dependent and -independent events

Influenza virus, the causative agent of the common flu, is a worldwide heal th problem with significant economic consequences. Studies of influenza vir us biology have revealed elaborate mechanisms by which the virus interacts with its host cell as it inhibits the synthesis of cellular proteins, evade s the innate antiviral response, and facilitates production of viral RNAs a nd 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 h ost cell. In this study, the cellular response to influenza virus infection was examined by monitoring the steady-state mRNA levels for over 4,600 cel lular genes. Infections with active and inactivated influenza viruses ident ified changes in cellular gene expression that were dependent on or indepen dent of viral replication, respectively. Viral replication resulted in the downregulation of many cellular mRNAs, and the effect was enhanced with tim e postinfection, Interestingly, several genes involved in protein synthesis , transcriptional regulation, and cytokine signaling were induced by influe nza 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 th e cellular metallothionein genes that may represent a protective response t o 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.