The University of Arizona’s Felicia Goodrum, PhD, and some of the nation’s most prominent human cytomegalovirus researchers have been awarded a five-year, $8.9 million collaborative grant to investigate how the virus lies dormant until it activates and poses life-threatening disease risk.
Dr. Goodrum, working with investigators at Louisiana State University Health Sciences Center in Shreveport and the lead organization, Oregon Health & Science University, will investigate different aspects of the virus-host interaction of the human cytomegalovirus (HCMV), one of nine human herpesviruses.
HCMV is a member of the herpesvirus family. Unlike many virus infections, HCMV infections are chronic – they never are cleared by the host. Instead, they hide their presence in dormancy. More than half of adults by age 40 have been infected with HCMV and most show no signs or symptoms. When HCMV is reactivated from dormancy, it poses life-threatening disease risks in individuals with compromised immune systems, including transplant, AIDS and cancer patients. HCMV infection also is the leading cause of infectious disease-related birth defects, affecting 1 in 150 live births in the United States.
Dr. Goodrum is an associate professor at the UA College of Medicine – Tucson, Department of Immunobiology, and a member of the UA BIO5 Institute. She will receive $1.3 million over five years. The grant, No. 1PO1Al127335-01, is funded by the National Institute of Allergy and Infectious Diseases.
"The University of Arizona's involvement in this collaborative effort is an outstanding example of the importance of basic science research and the role it plays in improving lives," said UA President Robert C. Robbins. "Dr. Goodrum has already had incredible impact in the biomedical sciences, and I look forward to learning the outcomes of this newest investigation."
Dr. Goodrum said each of the research teams will look at a different aspect of the virus-host interaction to understand how the virus “hijacks,” or manipulates, signaling pathways, the way cells communicate with one another, within its host, regulating how a host cell receives and transmits information from outside the cell’s environment to sense and respond to infection.
Their aim is to understand how HCMV can hijack its host’s biology allowing it to control entry and exit from dormant and active cycles, a key to its ability to exist in the human host.
Nationally renowned for her research on the virus, Dr. Goodrum was the first to discover the viral proteins that function to mediate the switch between dormant and actively replicative states. For this grant, Dr. Goodrum will seek to determine how proteins communicate with other “viral microRNAs” and proteins identified by the other project leaders to target the same host signaling pathways. Viral microRNAs are small nucleic acids that silence host gene expression, affecting virus infection by regulating virus or host gene expression to avoid the host defenses and/or to maintain latent and persistent infection.
“Understanding the virus-host interaction will represent a major step forward in understanding how we might target the dormant infection. No vaccine exists for the virus and current antivirals only target cells actively replicating the virus, so the virus is able to persist in dormancy,” said Dr. Goodrum.
Project leaders at OHSU are Jay Nelson, PhD, Dan Streblow, PhD, and Patrizia Caposio, PhD; Andrew Yurochko, PhD, is the project leader at Louisiana State University Health Sciences Center in Shreveport.
For related research please see: http://opa.uahs.arizona.edu/newsroom/news/2018/ua-researchers-create-first-roadmap-understand-ability-herpesvirus-remain-dormant
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