Host Gene Expression in Nasal and Blood Samples for the Diagnosis of Viral Respiratory Infection

Assessment of host gene expression is an emerging tool for the diagnosis of human infections. We compared nasal and blood samples for evaluation of the host transcriptomic response in children with acute respiratory syncytial virus (RSV), symptomatic and asymptomatic picornavirus (PV) infection, and virus-negative asymptomatic controls (Ctrls). RNA was extracted from nasal and blood samples and analyzed by microarray. Despite generally lower quality of nasal RNA, the number of genes detected in each sample type was equivalent. Nasal gene expression signal derived mainly from epithelial cells but also included a leukocyte contribution that was higher in samples from symptomatic children. The number of genes with increased expression in virus-infected children was comparable in nasal and blood samples, while nasal samples also had large numbers of genes with decreased expression, including many genes associated with ciliary function and assembly. Compared to symptomatic children, those with asymptomatic PV had fewer genes with increased or decreased expression in both sample types. Genes with increased expression in comparisons of symptomatic children versus Ctrls included genes associated with components of innate immunity and apoptosis. Children with RSV but not PV also had increased expression of genes related to the cell cycle. Using nested leave-one-pair-out cross-validation and supervised principal components analysis, we defined sets of genes whose expression patterns accurately classified subjects, with high area-under-the-curve values in receiver operating characteristic analysis. Our results support use of nasal samples to augment pathogen-based tests to diagnose viral respiratory infection. RNAs were extracted from whole blood and nasal swabs from 26 subjects, including 9 symptomatic cases who were infected with picornaviruses (sPV), 5 asymptomatic cases infected with picornaviruses (asPV), 6 symptomatic cases infected with respiratory syncytial virus (RSV) (2 cases had no blood specimens available), and 6 asymptomatic cases with no virus infection.