Antiviral Response in the Nasopharynx Identifies Patients With Respiratory Virus Infection

J Infect Dis. 2018 Mar 5;217(6):897-905. doi: 10.1093/infdis/jix648.

Abstract

Background: 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.

Methods: We performed RNA sequencing on human nasal epithelial cells following stimulation of the intracellular viral recognition receptor RIG-I. Next, we evaluated whether measuring identified host mRNAs and proteins from patient nasopharyngeal swabs could predict the presence of a respiratory virus in the sample.

Results: Our first study showed that a signature of 3 mRNAs, CXCL10, IFIT2, and OASL, predicted respiratory virus detection with an accuracy of 97% (95% confidence interval [CI], 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 area under the curve (AUC) values were: CXCL11 AUC = 0.901 (95% CI, 0.86-0.94); CXCL10 AUC = 0.85 (95% CI, 0.80-0.91).

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Biomarkers
  • Chemokine CXCL10 / metabolism
  • Chemokine CXCL11 / metabolism
  • Female
  • Gene Expression Regulation / immunology
  • Humans
  • Male
  • Nasopharynx / virology*
  • RNA, Messenger / genetics
  • RNA, Viral
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / virology
  • Virus Diseases / diagnosis
  • Virus Diseases / drug therapy*

Substances

  • Antiviral Agents
  • Biomarkers
  • CXCL10 protein, human
  • CXCL11 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL11
  • RNA, Messenger
  • RNA, Viral