Editors' ChoiceVirology

Going viral

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Science Translational Medicine  24 Jun 2015:
Vol. 7, Issue 293, pp. 293ec105
DOI: 10.1126/scitranslmed.aac7160

The genome, the microbiome, and now the virome... Viral infections are often short, but host-virome interactions can influence the host for decades, affecting everything from asthma to type I diabetes. Serological tests detect only one virus at a time, which is fine for the clinic, but provides only a glimpse at the big picture. Now, with just a drop of blood, Xu et al. have found a way to map an individual's entire viral infection history. The team used a synthetic peptide library representing proteins from all major human viruses to screen a patient's blood antibodies as a metric of viral exposure history in a process termed VirScan. The interplay of past infections and current immune response has now become visible.

VirScan begins with the design of a 200-mer oligonucleotide microarray encoding for peptides that span 200 viral proteomes. When these sequences were pooled and cloned into a single phage display format, a library representing a virome could be reacted against less than 1 µl of human serum to detect antibodies that have been generated by a prior or active antiviral immune response. VirScan achieved sensitivities of 95% or higher against known HIV and hepatitis C infections and matched commercial tests in distinguishing between closely related viral strains. Xu et al. then used this platform to conduct the first epidemiological study of its kind and showed geographical variation in viromes, with separate regions of the globe showing distinct responses to certain peptides. VirScan was less specific than some nucleic acid tests and detected lower levels of historical infection than what would be predicted in certain cases, likely due to a decrease in long-lived B cells and fewer antibodies to discover. Other limitations include an inability to detect epitopes that require posttranslational modifications or involve larger discontinuous sequences that the protein fragment library does not account for.

VirScan has clear potential as a new diagnostic that can greatly improve population-level analyses to better elucidate how previous viral infections affect current health. With VirScan's cheap and relatively easy production of the human virome, an individual's history of infection can one day take its place next to an x-ray in a patient's chart.

G. J. Xu et al., Comprehensive serological profiling of human populations using a synthetic human virome. Science 348, aaa0698 (2015). [Abstract]

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