New technology developed by Howard Hughes Medical Institute (HHMI) researchers 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, is an efficient alternative to existing diagnostics that test for specific viruses one at a time, according to the scientists.
With VirScan, researchers can run a single test to determine which viruses have infected an individual, rather than limiting their analysis to particular viruses. That unbiased approach could uncover unexpected factors affecting individual patients' health, and also expands opportunities to analyze and compare viral infections in large populations. The analysis reportedly can be performed for about $25 per blood sample.
“We've developed a screening methodology to basically look back in time in people's sera and see what viruses they have experienced,” says Stephen J. Elledge, an HHMI investigator at Brigham and Women's Hospital who led an international team that developed VirScan. “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.”
Dr. Elledge and his colleagues have already used VirScan to screen the blood of 569 people in the U.S., South Africa, Thailand, and Peru. Their study (“Comprehensive serological profiling of human populations using a synthetic human virome”) is described in Science.
VirScan works by screening the blood for antibodies against any of the 206 species of viruses known to infect humans. The immune system produces pathogen-specific antibodies when it encounters a virus for the first time, and it can continue to make 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 bacteriophage. Each bacteriophage manufactured one of the peptides and displayed the peptide on its surface. As a group, the bacteriophage 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 bacteriophage 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 bacteriophage that cling to them.
By sequencing the DNA of those bacteriophage, 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, either through infection or through vaccination. Dr. Elledge estimates it would take about 2–3 days to process 100 samples, assuming sequencing is working optimally. He is optimistic the speed of the assay will increase with further development.
Dr. Elledge says the approach his team has developed is not limited to antiviral antibodies. His own lab is also using it to look for antibodies that attack a body's own tissue 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.