Evaluation of Signature Erosion in Ebola Virus Due to Genomic Drift and Its Impact on the Performance of Diagnostic Assays
| Autor: | Michael A. Smith, Catherine E. Campbell, Bruce G. Goodwin, M. Holland, George W. Christopher, Jeffrey W. Koehler, Walter J. Berger, Timothy D. Minogue, Daniel Negron, Shanmuga Sozhamannan, Adrienne T. Hall, Mychal Ivancich |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
viruses
In silico lcsh:QR1-502 Genome Viral Biology medicine.disease_cause PSET Genome Western African outbreak Sensitivity and Specificity lcsh:Microbiology Virus Article Virology medicine Humans Diagnostic Errors signature erosion Ebolavirus Whole genome sequencing Ebola virus EBOV WGS qRT-PCR BioVelocity Genetic Drift virus diseases Hemorrhagic Fever Ebola Reverse transcription polymerase chain reaction Infectious Diseases Real-time polymerase chain reaction Molecular Diagnostic Techniques |
| Zdroj: | Viruses Volume 7 Issue 6 Pages 3130-3154 Viruses; Volume 7; Issue 6; Pages: 3130-3154 Viruses, Vol 7, Iss 6, Pp 3130-3154 (2015) |
| ISSN: | 1999-4915 |
| Popis: | Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes. |
| Databáze: | OpenAIRE |
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