Our next study was a quantum leap in sophistication. Our microarrays now contained over 4,600 cDNAs and our experimental system was more complex. This time, we profiled the cellular gene expression changes that occurred in HeLa cells infected with influenza virus, again analyzing two time points after infection [3] . In addition, we evaluated the cellular response to a heat-inactivated virus, allowing us to identify gene expression changes that were independent of viral replication. Genes involved in protein synthesis, transcriptional regulation, and cytokine signaling were induced by the replicating virus, and many of these changes suggested an active cellular antiviral response. Interestingly, viral replication also resulted in the down-regulation of many cellular genes, particularly at the later time point. The gene expression pattern induced by the inactivated virus included the induction of the cellular metallothionein genes, which may represent a protective response to virus-induced oxidative stress.