University of Arizona researchers have been awarded a $200,000 two-year seed grant by the Flinn Foundation through its Promoting Translational Research in Precision Medicine grants program to define the pulmonary virome and the role of Cytomegalovirus (CMV) persistence in the lung. The goal of this program is to foster collaborative efforts between physician-scientists and bench researchers in order to translate findings more rapidly to actual patient treatments.
The unique research team consists of UA Associate Professor of Medicine Ken Knox, MD, who specializes in pulmonary medicine and has a strong track record in clinical/translational research; UA associate professor of immunobiology, BIO5 member and biomedical researcher, Felicia Goodrum, PhD, who is an expert in CMV persistence; and UA associate professor of ecology and evolutionary biology and BIO5 member, Matthew Sullivan, PhD, an expert in viral metagenomics.
“Translational research—moving discoveries from the lab to patient care—is a crucial element of precision, or personalized, medicine as well Arizona’s bioscience strategy,” said Jack B. Jewett, Flinn Foundation president and CEO. “This exciting collaboration among Drs. Knox, Goodrum and Sullivan is an outstanding example of a potentially groundbreaking research project that could ultimately yield great benefits to human health.”
As a privately endowed, philanthropic organization, the Flinn Foundation is committed to improving the quality of life in Arizona to benefit future generations.
The human body is home to a vast number of bacteria, viruses and fungi that collectively make up the human microbiome. Much of our microbiome does not cause disease, but rather is critically important to maintaining human health. Recent studies in humans document the enormous impact bacteria have on normal health (e.g., obesity), disease states (e.g., diabetes, gastrointestinal disorders), and even behavior. The role of viruses, by contrast, represents uncharted frontiers for study.
Persistent viruses represent emerging health threats that contribute to chronic inflammation, cellular stress and cancer risk. In addition, latent viral coexistence is just beginning to emerge in association with age-related pathologies, including atherosclerosis, immune senescence and frailty. Health costs of persistent viral infections, whether chronic or latent, can be significant.
Drs. Knox, Goodrum and Sullivan will study CMV as a model of persistent viral infection upon which questions related to how to specifically prevent lung infections can be based. Manifestations of a disease state are influenced by how background host genetic traits drive immunological responses that interact with invading viruses. By using advanced informatics to analyze metagenomic data sets from the study, the team will investigate correlations between the presence of human CMV and the background virome.
Human CMV is one of eight human herpes viruses that infects 60-90 percent of the population worldwide and, like all herpes viruses, persists in the infected host indefinitely by way of a latent infection. CMV’s primary infection of healthy individuals is typically asymptomatic and, therefore, goes completely unnoticed. When CMV is reactivated from latency to an active state of replication, there are life-threatening disease risks in immunocompromised individuals, including transplant and cancer patients. CMV infection is also the leading cause of infectious disease-related birth defects, affecting 1 percent of live births in the United States.
Dr. Janko Nikolich-Zugich, MD, PhD, Bowman Professor and head, UA Department of Immunobiology, said, “This study is extremely important and timely, as known- and yet-to-be discovered viruses are undoubtedly influencing human health and contributing to disease states.”
Fernando Martinez, MD, UA Regents’ Professor and director of both the Arizona Respiratory Center and the BIO5 Institute, agreed, adding, “Defining the viruses present in the human lung will be an important step in expanding our knowledge base of the pulmonary virome. In addition, techniques used to identify viruses hold promise for rapid diagnostics and treatments.”
Other members of the study team (photo) at UA include PhD candidates Katie Caviness and Ann Gregory, senior research scientist Bonnie Poulos, Heidi Erickson, RN, and Lance Nesbit, MS. The current study also will examine viral reservoirs in the context of lung transplant and thus is likely to have broad implications for our understanding of pulmonary immunity and rejection.
The BIO5 Institute at the University of Arizona mobilizes top researchers in agriculture, engineering, medicine, pharmacy and science to find creative solutions to humanity’s most pressing health and environmental challenges. Since 2001, this interdisciplinary approach has been an international model of how to conduct collaborative research, and has resulted in improved food crops, innovative diagnostics, devices and promising new therapies. Learn more at BIO5.org.