Antiviral response detected via RNA-Seq from nasal swabs predicts respiratory viral infection

Despite the high burden of respiratory infection and the importance of early and accurate diagnosis, there is no simple diagnostic test to rule in viral infection as a cause of respiratory symptoms.

Yale University School of Medicine researchers performed RNA-Seq on human nasal epithelial cells following stimulation of the intracellular viral recognition receptor RIG-I. Next, they evaluated whether measuring identified host mRNAs and proteins from patient nasopharyngeal swabs could predict the presence of a respiratory virus in the sample.

The first study showed that a signature of three mRNAs, CXCL10, IFIT2, and OASL, predicted respiratory virus detection with an accuracy of 97% (95% C.I. 0.9-1.0), and identified proteins correlating with virus detection. In a second study, elevated CXCL11 or CXCL10 protein levels identified samples containing respiratory viruses, including viruses not on the initial test panel. Overall AUCs were: CXCL11 AUC=0.901 (95% CI 0.86-0.94); CXCL10 AUC=0.85 (95%CI 0.80-0.91). Patients were primarily older adults or young children, reflecting the population tested for respiratory viruses in our healthcare system.

rna-seq

Transcripts enriched by stimulation of primary human nasal epithelial cells with RIG-I ligand SLR14to mimic viral infection.Primary human nasal epithelial cells (HNEC) were transfected with SLR14for 1 hr, then incubated for 7 additional hours at 37°C, followed by RNA isolation and transcript analysis by RNASeq. Dots represent transcripts significantly different in control vs. SLR14stimulated nasal epithelial cells (p>0.05, log2FoldChange>1). Labels highlight transcripts examined in this study as potential nasopharyngeal biomarkers of viral respiratory infection.

Host antiviral mRNAs and single host proteins detectable using nasopharyngeal swabs accurately predict the presence of viral infection. This approach holds promise for developing rapid, cost-effective tests to improve management of patients with respiratory illnesses.

Landry ML, Foxman EF. (2017) Antiviral response in the nasopharynx identifies patients with respiratory virus infection. J Infect Dis [Epub ahead of print]. [article]

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