Resolving the Combinatorial and Cumulative Human Blood Virome

The human body is not entirely ‘human’. Instead, the composition of our body includes trillions of bacteria and viruses that co-exist with us and in turn change as we age. This project will focus on the human virome, meaning the composition of viruses that live in and on our bodies but usually do not make us sick.

Current estimates of the human virome indicate that for every one human cell, there are ~10 viral particles (or 380 trillion total) within the human body. Despite the ubiquity of these viruses, our knowledge about the commensal (or ‘tolerated’) virome, tolerogenic mechanisms, and response to pathogenic infection is in its infancy. Critically, approximately 1 in 30 individuals in our aging population are immunocompromised in the United States. Exemplified in organ/tissue transplants, immunodeficiencies yield dramatically different responses to otherwise tolerated infections, meaning the intersection of our aging population and the virome will continually increase the risk of life-threatening complications from viral infections normally controlled in homeostasis.

Here, we will develop new bioinformatic methodologies to study the composition, evolution, and impact of the virome on human health as a function of aging and development. Specifically, we will aggregate data from 1,000,000 individuals to study the blood virome with rich annotations of genetics, human phenotypes, and disease states. Our association analyses will resolve the virome’s impact on age-associated diseases, including autoimmune diseases and cancers. The result of this catalyst project will be the identification of specific viral species that could be targeted to improve human healthspan