PHILADELPHIA – For over a decade, scientists have studied the microbiome, the environment of microorganisms that live on and in the body, and how it affects health and disease. Much less is known about a part of the microbiome called the virome, the universe of viruses residing within our bodies. Now, researchers at the Perelman School of Medicine at the University of Pennsylvania have set out to identify, quantify, and classify those viruses so that future research can uncover how they affect human health. Ultimately, that could lead to new treatment and ways to prevent disease.
The endeavor, in collaboration with Penn Dental Medicine and Children's Hospital of Philadelphia (CHOP), is part of the National Institutes of Health's Human Virome Program and includes a $20-million grant to the research team spread over 5 years. The scientists, led by Ron Collman, MD, a professor of Pulmonary, Allergy, and Critical Care at Penn, and Frederic Bushman, PhD, the William Maul Measey Professor in Microbiology at Penn, will focus on viruses within 4 distinct areas: the gut, the upper-respiratory system and lungs, the mouth, and blood.
"This massive project will give the scientific community a solid foundation on which to build research," said Collman. "We can't begin to understand the interplay of these viruses with each other and other systems in the body until we have a full picture. Otherwise, it's like trying to put a puzzle together without all the pieces."
Viruses can live for a short period of time within our bodies, like influenza or SARS-CoV-2, or infect cells for years, like HIV and the varicella-zoster virus (which causes chickenpox and shingles). Both the short-lived (acute) and persistent viruses can cause symptoms, or they can be asymptomatic. But researchers agree that, since there are so many viruses present, some we know already and some we don't, there is a high probability that many viruses play a role in human health or disease even if they don't directly cause symptoms, said Collman. For example, a virus called cytomegalovirus (CMV) can be present in a person's body but usually causes no symptoms. However, research has shown that this virus plays a role in the aging process of the immune system.
"Our body is full of 'hitchhikers' like CMV that typically don't make us ill, but may play an important role in our biological processes," said Collman.
Beyond the viruses that live in human cells, the human body is also host to innumerable viruses that live in cells of the human microbiome, Collman said. How those viruses affect the microbiome human health is even less studied.
To track changes to the virome over time, researchers will use new samples as well as older samples from biobanks at Penn and CHOP.
Research into the microbiome accelerated rapidly over the last 15 years, said Bushman. He and his colleagues were among the first to paint a clear picture of the gut microbiome including its developmental stages in newborns. But, compared to viruses, bacteria are a lot easier to study, he said.
"Virome research lags behind microbiome research," said Bushman. "Bacteria are much bigger than viruses, and until recently, we did not have the technology, sequencing tools, and computational capacity to study viruses in the same way."
This project represents Phase 1 of the Human Virome Program. The NIH says Phase 2 will focus on viruses' interactions with their environment.
In addition to Collman and Bushman, other Penn Medicine researchers include Jim Lewis, Andrew Haas, Gary Wu, Hongzhe Lee, Steven Joffe, Holly Fernandez-Lynch, and Justin Clapp.
This research is supported by a grant from the National Institutes of Health Common Fund.
