From orphan virus to pathogen: The path to the clinical lab

Blood Systems Research Institute, San Francisco, CA, USA.
Current opinion in virology 10/2011; 1(4):282-8. DOI: 10.1016/j.coviro.2011.07.006
Source: PubMed


Viral metagenomics has recently yielded numerous previously uncharacterized viral genomes from human and animal samples. We review some of the metagenomics tools and strategies to determine which orphan viruses are likely pathogens. Disease association studies compare viral prevalence in patients with unexplained symptoms versus healthy individuals but require these case and control groups to be closely matched epidemiologically. The development of an antibody response in convalescent serum can temporarily link symptoms with a recent infection. Neutralizing antibody detection require often difficult cell culture virus amplification. Antibody binding assays require proper antigen synthesis and positive control sera to set assay thresholds. High levels of viral genetic diversity within orphan viral groups, frequent co-infections, low or rare pathogenicity, and chronic virus shedding, can all complicate disease association studies. The limited availability of matched cases and controls sample sets from different age groups and geographic origins is a major block for estimating the pathogenic potential of recently characterized orphan viruses. Current limitations on the practical use of deep sequencing for viral diagnostics are listed.

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Available from: Eric Delwart, Sep 30, 2015
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    • "Whereas “sequence-dependent” microbial detection methods, which are generally based on PCR or nucleic acid hybridisation, can only be used to target known pathogens, sequence-independent next generation sequencing (NGS) based approaches can potentially provide an ideal platform for identifying almost all known and unknown microbes present in any particular host organism [5], [7]–[9]. Coupled with innovative sample processing procedures, “metagenomics” applications of NGS [10] have already enabled the identification of novel pathogens through the rapid and comprehensive characterization of microbial strains and isolates within environmental and host tissue samples [9], [11]. "
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    • "For example, a study [20] identified two mutations within the core promoter of the telomerase reverse transcriptase in 50 of the 70 melanomas examined. Intergenic regions comprise 2009 0 500 1000 CumulaƟve PUBMED publicaƟons with 'exome' 1500 2000 2010 Year 2014 2013 2011 2012 "
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    Trends in Genetics 08/2013; 29(10). DOI:10.1016/j.tig.2013.07.006 · 9.92 Impact Factor
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