A host-based RT-PCR gene expression signature to identify acute respiratory viral infection.
Improved ways to diagnose acute respiratory viral infections could decrease inappropriate antibacterial use and serve as a vital triage mechanism in the event of a potential viral pandemic. Measurement of the host response to infection is an alternative to pathogen-based diagnostic testing and may improve diagnostic accuracy. We have developed a host-based assay with a reverse transcription polymerase chain reaction (RT-PCR) TaqMan low-density array (TLDA) platform for classifying respiratory viral infection. We developed the assay using two cohorts experimentally infected with influenza A H3N2/Wisconsin or influenza A H1N1/Brisbane, and validated the assay in a sample of adults presenting to the emergency department with fever (n = 102) and in healthy volunteers (n = 41). Peripheral blood RNA samples were obtained from individuals who underwent experimental viral challenge or who presented to the emergency department and had microbiologically proven viral respiratory infection or systemic bacterial infection. The selected gene set on the RT-PCR TLDA assay classified participants with experimentally induced influenza H3N2 and H1N1 infection with 100 and 87% accuracy, respectively. We validated this host gene expression signature in a cohort of 102 individuals arriving at the emergency department. The sensitivity of the RT-PCR test was 89% [95% confidence interval (CI), 72 to 98%], and the specificity was 94% (95% CI, 86 to 99%). These results show that RT-PCR-based detection of a host gene expression signature can classify individuals with respiratory viral infection and sets the stage for prospective evaluation of this diagnostic approach in a clinical setting.
Institute for Genome Sciences and Policy, Duke University School of Medicine, Durham, NC 27710, USA.
Aimee K
AK
Zaas
Thomas
T
Burke
Minhua
M
Chen
Micah
M
McClain
Bradly
B
Nicholson
Timothy
T
Veldman
Ephraim L
EL
Tsalik
Vance
V
Fowler
Emanuel P
EP
Rivers
Ronny
R
Otero
Stephen F
SF
Kingsmore
Deepak
D
Voora
Joseph
J
Lucas
Alfred O
AO
Hero
Lawrence
L
Carin
Christopher W
CW
Woods
Geoffrey S
GS
Ginsburg
D000328:Adult; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000472:pathogenicity; D007251:Influenza, Human / Q000175:diagnosis / Q000821:virology; D008297:Male; D012141:Respiratory Tract Infections / Q000175:diagnosis* / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D055815:Young Adult