cDNA microarray technology was applied to time course analysis of differentially expressed genes in A549 cells following human respiratory syncytial virus (HRSV) infection. Both up- and down-regulation of cellular genes were observed in a time-dependent manner. However, gene up-regulation prevailed over gene down-regulation. Virus infectivity was required as UV-inactivated virus failed to up-regulate/down-regulate those genes. At early times post-infection (0-6 h p.i.) 85 genes were up-regulated. Some of those genes were involved in cell growth/proliferation, cellular protein metabolism and cytoskeleton organization. Among the most strongly up-regulated genes at that time were the urokinase plasminogen activator (PLAU) and its receptor (PLAUR), a pleiotropic system involved in many biological processes, including chemotaxis and inflammation. Functionally related genes encoding the alpha- and beta-chains of several integrins were also up-regulated within the first 12 h of infection. Genes up-regulated between 6 and 12 h p.i. included interferon-stimulated genes (ISGs), genes related to oxidative stress and genes of the non-canonical NF-kappaB pathway. At later times, genes involved in the immune response became predominant among the up-regulated genes, most of them being ISGs. Different up-regulation kinetics of cytokine and cytokine-signalling-related genes were also observed. These results highlight the dynamic interplay between the virus and the host cell and provide a general picture of changes in cellular gene expression along the HRSV replicative cycle.
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