From a single drop of blood, researchers can now simultaneously test for more than 1,000 different strains of viruses that currently or have previously infected a person. Using a new method known as VirScan, researchers from Brigham and Women's Hospital (BWH) and Harvard Medical School tested for evidence of past viral infections, detecting on average 10 viral species per person. The new work sheds light on the interplay between a person's immunity and the human virome -- the vast array of viruses that can infect humans - with implications both for the clinic and for the field of immunology. The team reports its findings in Science on June 5.
"VirScan is a little like looking back in time: using this method, we can take a tiny drop of blood and determine what viruses a person has been infected with over the course of many years," said corresponding author Stephen Elledge, PhD, a principal investigator in the Division of Genetics at BWH and Gregor Mendel Professor of Genetics and of Medicine at Harvard Medical School. "What makes this so unique is the scale: right now, a physician needs to guess what virus might be at play and individually test for it. With VirScan, we can look for virtually all viruses, even rare ones, with a single test."
Classic blood tests, known as ELISA assays, can only detect one pathogen at a time. Additionally, ELISA assays have not been developed against all viruses, further limiting their usefulness. The team found the sensitivity and specificity of VirScan to be very similar to that of ELISA assays. The tests cost a comparable amount to run.
In the new study, Elledge and his colleagues tested blood samples from almost 600 people from Peru, the United States, South Africa and Thailand. The team developed and used a library of peptides - short protein fragments derived from viruses - representing more than 1,000 viral strains to find evidence of previous viral exposure. Rates of viral exposure varied by age, geographic location and HIV status, but the team found that a small number of peptides were recognized by the vast majority of people's immune systems. This pattern, suggesting that the immune systems of many individuals are hitting upon the same protein portion in a virus, could have important implications for understanding immunity.
VirScan may also help researchers find correlations between previous exposure to a particular virus and the development of a disease later in life. A connection between Epstein-Barr virus - one of the most common viruses seen in this study - and the risk of certain kinds of cancer is already known. The new method may help reveal other as-yet-unknown connections.
"A viral infection can leave behind an indelible footprint on the immune system," said Elledge. "Having a simple, reproducible method like VirScan may help us generate new hypotheses and understand the interplay between the virome and the host's immune system, with implications for a variety of diseases."
This work was supported by the National Institutes of Health (R01 DE018925-04, R37AI067073, DA033541, AI082630, N01-AI-30024, N01-AI-30024 and N01-AI-15422), the International AIDS Vaccine Initiative (UKZNRSA1001), African Research Chairs Initiative, the Victor Daitz Foundation, the Howard Hughes Medical Institute, the HIVACAT program, CUTHIVAC 241904, TRF Senior Research Scholar, the Thailand Research Fund; the Chulalongkorn University Research Professor Program, Thailand; and the National Science Foundation.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in Massachusetts and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $650 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in transplantation by performing a partial face transplant in 2009 and the nation's first full face transplant in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative as well as the TIMI Study Group, one of the premier cardiovascular clinical trials group. For more information, resources and to follow us on social media, please visit BWH's online newsroom.
Harvard Medical School has more than 7,500 full-time faculty working in 11 academic departments located at the School's Boston campus or in one of 47 hospital-based clinical departments at 16 Harvard-affiliated teaching hospitals and research institutes. Those affiliates include Beth Israel Deaconess Medical Center, Boston Children's Hospital, Brigham and Women's Hospital, Cambridge Health Alliance, Dana-Farber Cancer Institute, Harvard Pilgrim Health Care Institute, Hebrew Senior Life, Joslin Diabetes Center, Judge Baker Children's Center, Mass. Eye and Ear, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital and VA Boston Healthcare System.