Metatranscriptome Reveals Specific Immune and Microbial Signatures of Respiratory Syncytial Virus Infection in Children

Respiratory syncytial virus (RSV) is the most frequently detected respiratory virus in children with acute lower respiratory tract infection. Previous transcriptome studies have focused on systemic transcriptional profiles in blood and have not compared the expression of multiple viral transcriptomes. Here, we sought to compare transcriptome responses to infection with four common respiratory viruses for children (respiratory syncytial virus, adenovirus, influenza virus, and human metapneumovirus) in respiratory samples. Transcriptomic analysis showed that cilium organization and assembly were common pathways related to viral infection. Compared with other virus infections, collagen generation pathways were distinctively enriched in RSV infection. We identified two interferon-stimulated genes (ISGs), CXCL11 and IDO1, which were upregulated to a greater extent in the RSV group. In addition, a deconvolution algorithm was used to analyze the composition of immune cells in respiratory tract samples. The proportions of dendritic cells and neutrophils in the RSV group were significantly higher than those in the other virus groups. The RSV group exhibited a higher richness of Streptococcus than the other virus groups. The concordant and discordant responses mapped out here provide a window to explore the pathophysiology of the host response to RSV. Last, according to host-microbe network interference, RSV may disrupt respiratory microbial composition by changing the immune microenvironment. IMPORTANCE In the present study, we demonstrated the comparative results of host responses to infection between RSV and other three common respiratory viruses for children. The comparative transcriptomics study of respiratory samples sheds light on the significant roles that ciliary organization and assembly, extracellular matrix changes, and microbial interactions play in the pathogenesis of RSV infection. Additionally, it was demonstrated that the recruitment of neutrophils and dendritic cells (DCs) in the respiratory tract is more substantial in RSV infection than in other viral infections. Finally, we discovered that RSV infection dramatically increased the expression of two ISGs (CXCL11 and IDO1) and the abundance of Streptococcus.