P2-114 Interpreting Marginally Positive RT-qPCR Results Derived from Naturally-contaminated Samples: What Does It all Mean?

Tuesday, July 24, 2012
Exhibit Hall (Rhode Island Convention Center)
Rebecca Goulter-Thorsen, North Carolina State University, Raleigh, NC
You Li, North Carolina State University, Raleigh, NC
Jonathan Baugher, North Carolina State University, Raleigh, NC
Xi Chen, Clemson University, Clemson, SC
Angela Fraser, Clemson University, Clemson, SC
Lee-Ann Jaykus, North Carolina State University, Raleigh, NC
Introduction: Quantitative PCR (qPCR) and reverse transcription qPCR (RT-qPCR) have great potential to detect low levels of non-cultivable pathogens in food and environmental samples. Cloning and sequencing of amplicons is recommended for confirmation of presumptively positive results.  Nonetheless, amplifications with cycle threshold (Ct) values above 35 are common, difficult to interpret, and virtually impossible to confirm by sequencing. 

Purpose: To develop a DNA hybridization method to confirm presumptively positive RT-qPCR results obtained from environmental samples screened for evidence of human norovirus (HuNoV) contamination. 

Methods: RT-PCR (traditional and quantitative) was applied to RNA extracted using a silica-based guanadinium isothionate method, followed by amplification using primers JJV2F and COG2R targeting the ORF1-ORF2 junction (region B) of the HuNoV genome.  Probe Ring2P was used for qRT-PCR (45 cycles) and hybridization.  After optimization of the hybridization, serial dilutions of stool samples positive for HuNoV were subjected to RT-qPCR and traditional RT-PCR followed by dot blot hybridization to compare assay detection limits.  Both methods were applied to a subsample of 20 environmental samples collected from daycare facilities in the Carolinas previously tested for evidence of HuNoV contamination using RT-qPCR.

Results: As applied to serially diluted HuNoV-positive stool, RT-qPCR Ct values ranged from a low of 22 to a high of 38.  Detection limit of the RT-qPCR method was identical to that of RT-PCR followed by hybridization.  When both methods were applied to environmental samples all 10 samples previously screened negative for HuNoV by RT-qPCR were also negative by hybridization.  However, 10 samples previously classified as presumptively positive for HuNoV based on Ct values ranging from 36-44 were in fact negative by hybridization.  

Significance: The inability to confirm samples in the Ct range of 35-45 suggests cautious interpretation of RT-qPCR results and further highlights the need for confirmation.  DNA hybridization is a viable method to confirm the status of such samples when sequencing is not possible.