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Unbiased RNA Sequencing of Acute Respiratory Syncytial Virus Infection Reveals Gene Expression Signatures that Provide Insight into Pathogenesis
Monday, March 6, 2017: 2:30 PM
Rooms B308-B309 (Georgia World Congress Center, Building B)
Darrell L Dinwiddie, PhD, , , , ,
Rationale: Despite the enormous medical burden caused by respiratory viruses, many of the specific virus and host genetic factors that impact pathogenesis are still largely unknown or poorly understood. We sought to investigate the host response to respiratory syncytial virus (RSV) infections in clinical samples to understand the drivers of both acute clinical pathogenesis and long-term impacts, such as the development of asthma.

Methods: Nasopharyngeal swabs comprised of mixed cell populations at the active site of infection were collected from 32 pediatric patients with acute RSV infection. We used ribosomal RNA depletion and unbiased RNA sequencing which allowed the simultaneous detection of host gene expression and RSV infection. Samples were sequenced 2x75bp on an Illumina NextSeq 500 and sequences reads were mapped to the human genome using the TopHat 2 aligner. FPKM estimation of reference genes and transcripts and assembly of novel transcripts were conducted with Cufflinks 2.

Results: We identified 7,343 genes that were significantly expressed during acute RSV infection.  KEGG Pathway analysis revealed significant upregulation of pathways involved in innate immune response infection, ribosome function, oxidative phosphorylation, spliceosome and autoimmune disorders. Innate immune response genes with the highest level of expression included IFITM3, IFITM2, ISG15, IFITM1, CXCL8, IL1RN.

Conclusions: Host gene expression profiles obtained during acute RSV infections provide unprecedented insight into the mechanisms that cause pathogenesis and long-term impacts, such as the development of asthma, which may ultimately guide clinical treatment and management decisions for children with severe infections.