Chances are, you don't know all the viruses you've encountered throughout your life. Wouldn’t it be nice if you could just find out? According to a new study in Science, researchers have devised a blood test that can do just that by identifying the viruses that your immune system has fought in the past. The test is in its infancy, but it’s already giving us some insight into just how similar people’s immune systems are — despite the large geographic distances that can separate them.
Humans have "immunological memory"Humans have "immunological memory," meaning that our immune cells remember all the viruses we’ve encountered in the past. It's a biological system that helps speed up our immune response during future encounters with the same virus. Researchers tapped this memory tool to figure out virus infection histories for over 500 people across four continents.
First, researchers created a "viral library" from a public database of protein sequences belonging to all the viruses that are known to infect humans. The main step in this process was introducing lab-made pieces of virus DNA into "bacteriophages," or viruses that infect bacteria. Thanks to this genetic engineering trick, the bacteriophages displayed a synthetic representation, or marker, of a given virus’s proteins on their surface — proteins that a person's immune system would only recognize if they had already encountered the virus. The researchers then mixed the bacteriophages with a sample of the participants’ blood. By identifying the virus markers that a participant’s antibodies stuck to, they were able to infer which viruses had previously infected them.
"We've created this huge pond full of all possible human viruses."
"You could think of it as we're fishing with bait — the bait is the patient's antibodies — and we've created this huge pond full of all possible human viruses," says Benjamin Larman, an immunopathologist at Johns Hopkins University and a co-author of the study. "We're using the patient's antibodies to pull out the viruses that they've been infected with."
On average, researchers detected immune system responses to 10 viral species per person, though two individuals displayed antibody responses to 84 species of viruses. Larman and his team also found that the number of viruses detected by a person's immune system varies according to age, HIV status, and geography. The virus that came up the most often was the Epstein-Barr virus, which is responsible for mononucleosis.
Two individuals displayed antibody responses to 84 species of viruses
At its heart, this study is a technology development paper, Larman says. Doing this a few years ago wouldn’t have been possible, but recent advances in DNA synthesis and sequencing have allowed researchers to create this new method, called "VirScan." The study is "a great demonstration of the power of new DNA synthesis and sequencing technologies to address biological questions at a very large scale not previously possible," says Timothy Lu, a biological engineer at MIT, who didn’t participate in the study. The work also presents "a powerful platform for studying the human antiviral repertoire," he says.
The test is cheap — analyzing a blood sample costs $25 — and 100 samples can be processed in a single week. But VirScan won’t be available to the public for a number of years; the FDA regulatory process requires validation through further experiments. And, in truth, this might not be the type of test that gets used by doctors right away. For many, knowing which viruses you’ve survived will be a novelty. That said, the test will certainly help researchers get a better understanding of ways in which humans respond to virus infection. And eventually, Larman and his team would like to create a simpler test that could be used in a clinic to improve infection diagnosis. But again, that's a long way off — Larman estimates that general adoption of the technology is roughly five to 10 years out.
"[Can't] use the current library to identify new viruses."
The study was small, which means that some findings might change as more people take the test. In addition, as researchers discover new viruses, the library will grow and yield more data. This is a huge strength, but it also demonstrates one of the study's main limitations. "We can only find responses to viruses that we already know about," Larman says. "So we're not going to be able to use the current library to identify new viruses."
There's a lot to be learned from the library in its current form, however. Being able to look at infections from people around the world means that researchers could ask if geography has an impact on people's responses to various infections. For instance, a researcher could ask if antibodies belonging to people in Asia stick to the same markers on a virus’s surface compared with people in Canada. Researchers could also try to see if the occurrence of certain viruses correlate with other types of disease, Larman suggests.
This geographical bent is what Larman finds most intriguing about the work. So far, the study shows that antibodies that humans generate operate "in almost indistinguishable ways, on average" in response to a virus. "There are some exceptions but the similarity is really quite striking, whether they're in Africa, Thailand, or the United States," he says. "People have seen glimpses of this in the past, but this is certainly the most comprehensive analysis of this phenomenon."
Correction: A previous version of this article stated that bacteriophages are bacteria that infect viruses. This is incorrect. Bacteriophages are viruses that infect bacteria. We regret the error.