Time-course of transcriptome response to respiratory syncytial virus infection in lung epithelium cells.

Abstract

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infection in infants. Winter outbreaks in Chile result in 5% of infected children hospitalized, with 0.01% mortality. Increased evidence indicates that viral and host factors modulate the severity of infection. Using DNA microarrays, we characterized the genome-wide transcriptional response of lung mucoepidermoid cells (NCI-H292) at 0, 24, 48, 72 and 96 hours post-infection (hpi) with a single dose of RSV/A. During the whole studied period, a bi-phasic gene expression profile was observed by a total of 330 differentially expressed genes. About 60% of them were up-regulated between 24-72hpi and then turned-off at 96hpi. This transient, early gene expression pattern was significantly enriched in biological processes like interferon signaling, antigen processing and presentation, double-stranded RNA binding and chemokine activity. We detected 27 common genes up-regulated between 24-72hpi, from which IFIT1, IFI44, MX1, CXCL11 and OAS1 had the highest expression. The second pattern comprised over 120 genes, which remained silenced until 72hpi, but were steeply up-regulated by 96hpi. Biological processes of this late-response profile included cell cycle division and microtubule cytoskeleton organization. Conversely, the genes belonging to virus response pathway showed a decreased expression at 96hpi. We conclude that RSV induces an early innate immune activation profile response until 72hpi. Thereafter, the viral response is inhibited, leading to host cell recovery. The presented cellular model allows to study the specific pathways involved in elimination of infection at prolonged time intervals and their subsequent analysis in severe RSV disease of infants and/or older adults.