Virologists estimate that there are some 320,000 unique mammalian viruses, and likely exponentially more existing on the planet today. Determining an accurate number would require billions more dollars and a great deal more manpower than is currently given to the study of viruses. Though a handful of viruses live in and on our bodies at all times—known as the virome—not all of them make us ill; just as often, they lie dormant. Many virus functions remain mysterious to scientists, such as how they enter a cell or replicate, though existing test advances, like the VirScan blood test, can tell you any infection you’ve ever had.
However, a brand-new test developed by researchers at Washington University in St. Louis can now detect virtually any virus known to affect humans and animals. Called ViroCap, this test can also detect “novel” viruses not yet identified, as long as they share a few genetic characteristics with known viruses.
According to Kristine Wylie, assistant professor of pediatrics at the university's McDonnell Genome Institute, and co-author of the study, published in Genome Research, “One of the exciting things of using this high-throughput sequencing is the amount of data we are able to generate in a short amount of time.”
Researchers developed the test by condensing one billion viral genetic base pairs to 200 million usable sequences. Then they took a snippet of each sequence, and made those snippets into “probes” that can turn up a genetic match in patient samples.
Because of its vast database of viruses, ViroCap is more sensitive than the standard polymerase chain reaction (PCR) tests commonly used, consolidating those 2 million RNA and DNA gene sequences into a single assay. Researchers can scan the virus genetic sequences and look for a match from conserved genes that have been gathered in public repositories such as the Viral Genome Project.
ViroCap has the capacity to detect a vast array of viruses, from the big, bad scary ones such as Ebola or SARS, to the everyday rhinoviruses and noroviruses that cause colds and gastrointestinal flu. It’s so sensitive, Wylie says, that it can also detect genetic variants of a virus, which regular tests simply can’t catch.
Researchers tested ViroCap on the blood and stool samples of a small group of children with unexplained fevers. In this group, standard testing had found 11 viruses. ViroCap found seven more. In total, for all samples, ViroCap was able to find 52 percent more viruses than standard tests.
“There are practical clinical applications for viruses that don’t get diagnosed,” Wylie says. “A known virus might turn up in an unexpected place. Clinicians might find a virus they never thought could be causing a disease. When we did a study of kids with fever, for example, one patient in that study had a virus we never would have looked for in the blood.”
People with unexplained fevers are also often prescribed antibiotics if a virus can’t be detected. Wylie says ViroCap could potentially cut down on the overuse of antibiotics.
With modifications of the test, researchers could also begin to look for drug-resistant mutations, and mutations in regions that would indicate whether a vaccine would or would not be as effective. It may also help researchers understand why some people carry around viruses asymptomatically. “We found on average that people carried about 5.5 different viral genera that could cause disease in certain people,” Wylie says. “In our study of kids, we found that rhinoviruses that cause colds were just as common in kids that didn’t have colds as those that did. So we need to understand what circumstances cause some to be symptomatic.”
What’s more, ViroCap can help to add previously unidentified viral DNA to the database of known viruses. “The more genome coverage we have, the more we can learn,” she says.
In that spirit, the team has made their test available to any researcher interested in using it because of its wide potential. It's likely still a long way from being in use. “Research-wise,” Wylie says, “it’s a whole new world. ViroCap is turning up the magnification [on viruses].”