Monday, June 10, 2013

Loyola Researchers Discover How Hepatitis C Virus Manipulates Liver Cells

MAYWOOD, Ill. – Hepatitis C virus (HCV) has infected more than 170 million people worldwide. Approximately 80 percent of infections lead to chronic illness including fibrosis, cirrhosis, cancer and also hepatic iron overload. A new study completed by researchers at Loyola University Chicago Stritch School of Medicine reveals that HCV not only alters expression of the iron-uptake receptor known as transferrin receptor 1 but that TfR1 also mediates HCV entry.

"We have not yet discovered a cure for Hepatitis C, however discovering the relationship between HCV and TfR1 sheds more light on the complex, multistep process required for the virus to get into liver cells," said senior author Susan L. Uprichard, PhD, virologist and director of Hepatology Research, Loyola.

“This new knowledge reveals important insight into how the virus interacts with and changes our liver cells for its own benefit. As such, it may facilitate the development of entry inhibitors or treatments for HCV-associated iron overload."

The research findings  could also potentially be used in the clinical setting for the care of patients not only for those with chronic liver disease but also for post-liver-transplant care where it might help prevent infection of a new liver or at least slow disease progression.  Uprichard said her HCV research lays important groundwork. “This research is like finding one of the four corners of a puzzle,” she said. “It creates a key building block toward finding a medical solution to Hepatitis C.”

The new study is part of a project initially directed at understanding how HCV may disrupt cellular iron homeostasis. “TfR1 plays a role in HCV infection at the level of glycoprotein-mediated entry, acts after CD81 and is possibly involved in HCV particle internalization,” said Danyelle Martin, the first author of the study who performed this research as part of her PhD work at University of Illinois at Chicago (UIC) and is now manager of the newly established Clinical Research Office Biobank at Loyola University Medical Center. “More studies will need to be done to determine if and how the interaction between TfR1 and HCV leads to the hepatic iron overload seen in HCV infected patients.”

Results of the HCV study were published in the Proceedings of the National Academy of Sciences (PNAS) the week of June 10.

"The Hepatitis C virus is fascinating and complex; we are still learning about the biology of the virus, including the liver cell factors the virus needs to replicate and how these interactions cause the specific liver dysfunction observed in patients,” said Uprichard, who also began the research while at UIC.

Uprichard and Martin are members of Loyola’s Division of Hepatology headed by Scott Cotler, MD, and the Clinical Research Office led by Thomas Layden, MD.

Together with Harel Dahari, PhD, a mathematical modeler and another member of the Division of Hepatology, Dr. Uprichard co-directs a new Program for Experimental and Translational Modeling currently being established at Loyola to promote interdisciplinary research.

About Loyola University Health System

Loyola University Health System (LUHS) is part of Trinity Health. Based in the western suburbs of Chicago, LUHS is a quaternary care system with a 61-acre main medical center campus, the 36-acre Gottlieb Memorial Hospital campus and more than 30 primary and specialty care facilities in Cook, Will and DuPage counties. Loyola University Medical Center’s campus is conveniently located in Maywood, 13 miles west of Chicago’s Loop and 8 miles east of Oak Brook, Ill. At the heart of the medical center campus is a 559-licensed-bed hospital that houses a Level 1 Trauma Center, a Burn Center and the Ronald McDonald® Children's Hospital of Loyola University Medical Center. Also on campus are the Cardinal Bernardin Cancer Center, Loyola Outpatient Center, Center for Heart & Vascular Medicine and Loyola Oral Health Center as well as Loyola University Chicago Stritch School of Medicine, Loyola University Chicago Marcella Niehoff School of Nursing and the Loyola Center for Fitness. Loyola's Gottlieb campus in Melrose Park includes the 255-licensed-bed community hospital, the Professional Office Building housing 150 private practice clinics, the Adult Day Care, the Gottlieb Center for Fitness, Loyola Center for Metabolic Surgery and Bariatric Care and the Loyola Cancer Care & Research at the Marjorie G. Weinberg Cancer Center at Melrose Park.

Trinity Health is a national Catholic health system with an enduring legacy and a steadfast mission to be a transforming and healing presence within the communities we serve. Trinity is committed to being a people-centered health care system that enables better health, better care and lower costs. Trinity Health has 88 hospitals and hundreds of continuing care facilities, home care agencies and outpatient centers in 21 states and 119,000 employees.