With the aid of a five-year, $20 million research grant from the National Institutes of Health, a Vanderbilt University Medical Center research team will venture to broadly characterize the role of viruses in human health and disease. The grant will help establish the Vanderbilt-coordinated Virus Characterization Center, or V2C2.
“Human viruses are largely understudied, with most research historically focusing only on pathogenic viruses that cause obvious clinical disease, while the vast majority of viruses that reside in us without causing disease remain poorly understood,” said one of four principal investigators for the project, Suman Das, PhD, research associate professor of Medicine in the Division of Infectious Diseases, who also serves as V2C2’s administrative lead.
Under the Human Virome Program, launched last year by the NIH Common Fund, V2C2 will figure as one of five research centers seeking to characterize the human virome — the collection of viruses in or on the human body — using diverse research cohorts across human lifespan, with participants studied repeatedly over a period of years. These centers will work in concert with research teams at other institutions having the allied aims of elucidating the interactions between the human host and the virome and developing tools, models and methods to interrogate and annotate the human virome.
“Our center builds on an estimable track record of virus research at VUMC,” said another principal investigator for V2C2, Ravi Shah, MD, professor of Medicine in the Division of Cardiovascular Medicine. “V2C2 will seek to delineate the range of viruses that exist within human tissues and plasma — causing symptoms or not, passing through or persisting in the body, whether in human cells or in various constituents of the human microbiome. With our partners across the Human Virome Program, we hope to answer new and important questions concerning the role of viruses in human health and disease.”
The two remaining principal investigators for V2C2 are epidemiologists Kari North, PhD, from the University of North Carolina at Chapel Hill and Susan Fisher-Hoch, MD, from the UTHealth Houston School of Public Health in Brownsville.
Das and Shah outlined some of the hypotheses shaping the pioneering NIH program.
• Nonpathogenic viruses likely play important roles in human health and disease — like how the study of the human microbiome has revealed important roles for bacteria.
• Viral persistence and integration into the human genome, even without symptoms, may significantly impact phenotypes (that is, observable traits) and health outcomes over time.
• There are likely important differences in host responses to the ambient virome that drive differences in human phenotypes.
• Understanding the healthy human virome could provide a basis for eventual discovery of novel biomarkers for health and disease and new therapeutic approaches.
V2C2 will utilize two well-established cohorts to study the human virome: the Cameron County Hispanic Cohort (CCHC) and VUMC’s Childhood Allergy and the Neonatal Environment – Viruses study cohort (CANOE-VU). CCHC includes individuals ages 8 to 90 years from a low-income Hispanic/Latino population at the U.S.-Mexico border, with approximately 93% being Mexican American. Participating from this cohort will be approximately 1,750 individuals with bio samples spanning up to 20 years and 500 individuals who will provide prospective samples over approximately four years. CANOE-VU, a study led by Tina Hartert, MD, MPH, professor of Medicine and Pediatrics, includes about 200 children followed from birth through age 5, recruited from VUMC obstetrical and nurse midwife practices. This birth cohort provides unique access to maternal-child samples across early development, including samples like placental tissue and breast milk.
“Together,” Das said, “these cohorts offer diversity across sex, sociodemographics, ancestry and geography, while providing both retrospective and prospective sampling approaches to facilitate rapid project deployment and cost-efficient analysis of the human virome.”
A central premise of the Human Virome Program is that the virome interacts significantly both with the host immune system and the human microbiome. Key research methods used by V2C2 will include novel integrated whole metagenomic/metatranscriptomic sequencing methods developed by Das’s group to assess DNA and RNA viruses, viral isolation and tropism studies (which reveal tissue preferences of viruses), and various methods to characterize host response, such as host genomic integration analysis, analysis of the inflammatory state, and mucosal response studies.
Other VUMC researchers participating in V2C2 are Simon Mallal, MBBS, Jane Freedman, MD, Jennifer Below, PhD, Eric Gamazon, PhD, MS, Tina Hartert, MD, MPH, Seesandra Rajagopala, PhD, Ellen Wright Clayton, MD, JD, Bradley Malin, PhD, Meghan Shilts, MS, Suman Pakala, ME, Kristen Ogden, PhD, Staci Sudenga PhD, MPH, Bhuminder Singh, PhD, Christian Rosas-Salazar, MD, MPH, and Siyuan Ma, PhD.
V2C2 is supported by NIH grant U54-AG089326.
