Multi-Site Effort to Understand Viral Influences on Human Health

For more than ten years, researchers have been investigating the microbiome, the ecosystem of microorganisms that inhabit the body, and its impact on health and disease. However, significantly less is understood about a component of the microbiome known as the virome, which encompasses the array of viruses present in human bodies.

Recently, scientists at the Perelman School of Medicine at the University of Pennsylvania have embarked on a project to identify, quantify, and classify these viruses, paving the way for future studies to explore their influence on human health. This research could ultimately lead to new treatments and preventive measures for various diseases.

This initiative, in partnership with Penn Dental Medicine and the Children’s Hospital of Philadelphia (CHOP), is part of the National Institutes of Health’s Human Virome Program and is supported by a $20 million grant allocated to the research team over five years.

The scientists are 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. Their research will concentrate on viruses in four specific areas: the gut, the upper respiratory system and lungs, the oral cavity, and the bloodstream.

This massive project will give the scientific community a solid foundation on which to build research. We cannot 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 is like trying to put a puzzle together without all the pieces.”

Ron Collman, MD, Professor, Perelman School of Medicine, University of Pennsylvania

Viruses can exist in human bodies for varying durations; some, like influenza or SARS-CoV-2, are short-lived, while others, such as HIV and the varicella-zoster virus (which leads to chickenpox and shingles), can persist for years.

Both acute (short-lived) and chronic viruses can manifest symptoms or remain asymptomatic. Researchers, including Collman, concur that the vast array of viruses some known and others yet to be identified likely influences human health and disease, even in the absence of direct symptoms.

For instance, cytomegalovirus (CMV) may reside in an individual without causing noticeable symptoms, yet studies indicate that it contributes to the aging of the immune system.

Our body is full of ‘hitchhikers’ like CMV that typically do not make us ill, but may play an important role in our biological processes.”

Ron Collman, MD, Professor, Perelman School of Medicine, University of Pennsylvania

In addition to the viruses residing within human cells, the human body also harbors countless viruses that inhabit the cells of the human microbiome, according to Collman. The impact of these viruses on the microbiome and human health remains significantly underexplored.

To monitor changes in the virome over time, researchers will utilize both new samples and older samples sourced from biobanks at Penn and CHOP.

Research on the microbiome has advanced rapidly over the past 15 years, noted Bushman. He and his colleagues were among the pioneers in elucidating the gut microbiome, including its developmental stages in infants. However, he pointed out that studying bacteria is considerably easier than studying viruses.

Virome research lags behind microbiome research. 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.”

Frederic Bushman, William Maul Measey Professor, University of Pennsylvania

This project constitutes Phase 1 of the Human Virome Program. According to the NIH, Phase 2 will concentrate on the interactions between viruses and their environment.