In a new peer-reviewed research study published in the Public Library of Sciences (PLoS Pathogens), University of Arizona Health Sciences researcher Felicia Goodrum, PhD, an associate professor in the Department of Immunobiology at the UA College of Medicine – Tucson, has identified how the cytomegalovirus is able to go latent and undetected, then become active and lead to life-threatening health risks.
Dr. Goodrum is a member of the BIO5 Institute and her lab studies cytomegalovirus. The virus is known as CMV and is a part of the herpes virus family. It poses a life-threatening risk for those with weak immune systems, the elderly and those fighting diseases like AIDS and cancer. In the unborn, CMV presents a risk in pregnancy and is the leading cause of infectious-disease related birth defects in babies.
In the general population, people are typically infected as children and never know it because it does not cause any disease or symptoms. Once people are infected, they will carry the virus their whole life as a dormant or latent infection.
In previous research, Dr. Goodrum identified a novel molecular switch in CMV made up of two antagonistic proteins working to counteract one another, one protein working to suppress replication and the other protein working to overcome this suppression for reactivation. This was the first indication of how entry into and exit from latency might be controlled. Defining the mechanism required identifying the targets of these proteins in the host cell.
Thanks to the new findings published in the study, “Opposing Regulation of the EGF Receptor: A Molecular Switch Controlling Cytomegalovirus Latency and Replication,” Dr.
Goodrum and her team have identified how the virus and its antagonistic viral proteins were both targeting the epidermal growth factor receptor, or EGFR, essentially hard-wiring itself into the host’s biology, making it able to sense and respond to changes within the host, or human body.
EGFR is essential for many fundamental cellular processes like division, wound repair and the development of new blood vessels, collaborating at the molecular level with the organ system to protect and help maintain the human body in balance.
“We have never understood molecularly how CMV or other persistent viruses establish and maintain a latent state or how they exit latency to replicate again. This work establishes some fundamental molecular principles that explain the ability of the virus to integrate itself into human biology to control these processes,” said Dr. Goodrum.
Dr. Goodrum collaborated with BIO5 colleague Joyce Schroeder, PhD, UA professor of molecular and cellular biology and a member of the UA Cancer Center, and with Scott Terhune, PhD at the Medical College of Wisconsin, for the study.
Like many viral infections and diseases, there are currently no vaccines and antiviral treatments for CMV are limited. Understanding how CMV latency is controlled could translate to the development of treatment for a wide range of viral diseases.
“This research discovery will advance the way we approach the design of strategies to control the virus in susceptible individuals,” said Dr. Goodrum. “Before we can approach these human challenges, we need to know more about how the virus impacts the cell or host by targeting EGFR. What are the effects of this interaction on host biology and how does this benefit the virus?” said Dr. Goodrum.
About the University of Arizona BIO5 Institute
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 and devices and promising new therapies. Learn more at http://BIO5.org
About the University of Arizona Health Sciences
The University of Arizona Health Sciences is the statewide leader in biomedical research and health professions training. The UA Health Sciences includes the UA Colleges of Medicine (Phoenix and Tucson), Nursing, Pharmacy and Mel and Enid Zuckerman College of Public Health, with main campus locations in Tucson and the growing Phoenix Biomedical Campus in downtown Phoenix. From these vantage points, the UA Health Sciences reaches across the state of Arizona and the greater Southwest to provide cutting-edge health education, research, patient care and community outreach services. A major economic engine, the UA Health Sciences employs almost 5,000 people, has nearly 1,000 faculty members and garners more than $126 million in research grants and contracts annually. For more information: http://uahs.arizona.edu/