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New Technology Reveals Viral Infection History in Single Drop of Blood

$25 assay looks for multiple viruses simultaneously

New technology developed by researchers at the Howard Hughes Medical Institute in New York City makes it possible to test for current and past infections with any known human virus by analyzing a single drop of a person’s blood. The method, called VirScan, offers an alternative to existing diagnostics that test for specific viruses one at a time.

With the new analysis, scientists can run a single test to determine which viruses have infected an individual, rather than limiting their assessments to particular viruses. The analysis costs about $25 per blood sample.

Dr. Stephen J. Elledge of Brigham and Women’s Hospital led the development of VirScan. “We’ve developed a screening methodology to basically look back in time in people’s [blood] sera and see what viruses they have experienced,” he says. “Instead of testing for one individual virus at a time, which is labor intensive, we can assay all of these at once. It’s one-stop shopping.”

Elledge and his colleagues used VirScan to screen the blood of 569 people in the U.S., South Africa, Thailand, and Peru. They reported their findings in the June 5 issue of Science.

VirScan works by screening the blood for antibodies against any of the 206 species of viruses known to infect humans. The body’s immune system ramps up the production of pathogen-specific antibodies when it encounters a virus for the first time, and it can continue to produce those antibodies for years or decades after it clears an infection. That means VirScan not only identifies viral infections that the immune system is actively fighting, but also provides a history of an individual’s past infections.

To develop the new test, Elledge and his colleagues synthesized more than 93,000 short pieces of DNA encoding different segments of viral proteins. They introduced those pieces of DNA into bacteria-infecting viruses called bacteriophages. Each bacteriophage manufactured one of the protein segments –– known as a peptide –– and displayed the peptide on its surface. As a group, the bacteriophages displayed all of the protein sequences found in the more than 1,000 known strains of human viruses.

Antibodies in the blood find their viral targets by recognizing unique features, known as epitopes, that are embedded in proteins on the virus surface. To perform the VirScan analysis, all of the peptide-displaying bacteriophages are allowed to mingle with a blood sample. Antiviral antibodies in the blood find and bind to their target epitopes within the displayed peptides. The scientists then retrieve the antibodies and wash away everything except for the few bacteriophages that cling to them. By sequencing the DNA of those bacteriophages, they can identify which viral protein pieces were grabbed onto by antibodies in the blood sample. That tells the scientists which viruses a person’s immune system has previously encountered, through either infection or vaccination.

Elledge estimated it takes about 2 to 3 days to process 100 samples, assuming that the sequencing is working optimally. He is optimistic that the speed of the assay will increase with further development.

To test the method, the team used it to analyze blood samples from patients known to be infected with particular viruses, including human immunodeficiency virus (HIV) and hepatitis C virus. “It turns out that it works really well,” Elledge said. “We were in the sensitivity range of 95 to 100 percent for those, and the specificity was good — we didn't falsely identify people who were negative. That gave us confidence that we could detect other viruses.”

Elledge said that the approach his team has developed is not limited to antiviral antibodies. His laboratory is also using it to look for antibodies that attack a person’s own tissues in certain autoimmune diseases that are associated with cancer. A similar approach could also be used to screen for antibodies against other types of pathogens.

Source: Howard Hughes Medical Institute; June 4, 2015.

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