Can’t remember every viral infection you’ve ever had? Don’t worry, your blood can. A new test surveys the antibodies present in a person’s bloodstream to reveal a history of the viruses they’ve been infected with throughout their life. The method could be useful not only for diagnosing current and past illnesses, but for developing vaccines and studying links between viruses and chronic disease.
“This is really a technical tour de force,” says immunologist Hidde Ploegh of the Massachusetts Institute of Technology in Cambridge, who was not involved in the new work. But others point out that it's unclear how many past infections the new technology misses.
Now, researchers wondering whether a patient has a particular viral infection—from herpes and flu to the AIDS virus—test blood samples for one pathogen at a time. Many tests look for antibodies, proteins the immune system produces to recognize invaders, while others hunt for the virus’s own genetic material. Some assays can measure the presence or absence of longer-lasting antibodies that can linger for decades after an infection.
Researchers led by biologist Stephen Elledge of Brigham and Women's Hospital in Boston and Harvard Medical School wanted to develop a test that could look at every current or past infection in one fell swoop. They first assembled a library of almost a hundred thousand synthetic protein fragments, each of them representing a section of a virus that an antibody might recognize. When the proteins are added to a drop of blood, antibodies attach to matching fragments; researchers can isolate the antibodies and, from the fragments they paired up with, determine which viruses someone has been infected with and what antibodies their body generated in response.
The new test, dubbed VirScan, “allows scientists to ask questions that just couldn’t be asked before,” Elledge says. “You can compare groups of people—young and old or those with a disease and those without—and see whether there’s a difference in their viral histories.” For instance, VirScan could help determine whether viral infections can trigger diabetes or chronic fatigue syndrome.
Elledge and colleagues used VirScan on more than 500 people from the United States, Thailand, South Africa, and Peru, some of them infected with HIV. On average, they report online today in Science, most people had antibodies for about 10 previous viral infections, although those with HIV and who lived outside the United States averaged more. Throughout all populations, common viruses including the herpes virus and rhinoviruses (which cause the common cold) topped the list. Surprisingly, many people had generated the exact same antibodies to infections; researchers believed people's immune responses to be more diverse, Elledge says. That observation could inform future vaccine development, he says.
Whether the test really catches everything is up for debate, however, says microbiologist Vincent Racaniello of Columbia University. “Before we view this as a definitive definition of what people have been infected with, we need to be sure it’s a comprehensive picture,” he says. “Right now, I don’t think it is.” Racaniello points out that VirScan didn’t identify as many people as he would expect with antibodies for noroviruses and rotaviruses, which cause large numbers of intestinal infections. This could be because antibodies for these viruses don’t stick around for as long as others—although researchers have shown that, in general, most antibodies last a lifetime—or because of technical caveats of the test.
Elledge admits that, for now, VirScan might miss some viruses, because they’re too small or contain certain modifications that the fragment library can’t include. “We know that we’re probably missing a little bit,” he says. “But we’re still detecting a lot.”
“The work stands out by its breadth and technological innovation,” Ploegh says. “But if you ask an immunologist how many viruses or pathogens you’ve fought in your lifetime and what signatures of those infections remain, the results of this paper wouldn’t be a surprise." The technology's real value lies in the new questions scientists can answer, he says. "For sketching the natural history of the human species interacting with viruses, I think this is a very important tool.”
VirScan has yet to be scaled up for commercial use but Elledge hopes it won't cost much more than existing tests that only look at one pathogen at a time. If so, it could even be used for routine screening at annual physicals, he says. “You could give a drop of blood every few years and they can run it to see if you have any new infections,” he says. This could help diagnose viruses like hepatitis C, which people often don’t know they have.