Can the Black Death from 14th century Europe provide insights into today’s diseases of HIV and hepatitis C?
The Black Death swept Europe in the 14th century eliminating up to half of the population but it left genetic clues that now may aid a University of Cincinnati (UC) researcher in treating HIV patients co-infected with hepatitis C using an anti-retroviral drug therapy.
Kenneth Sherman, MD, PhD, Gould Professor of Medicine, says he will look at the blood samples of nearly 3,000 patients, primarily individuals with hemophilia, who were exposed to HIV during the early 1980s and late 1990s, to see if an inherited genetic variant that protects against HIV might also help prevent injury from Hepatitis C and other liver diseases.
Sherman, also director of the Division of Digestive Diseases in the UC College of Medicine, recently received a $2 million grant from the National Institutes of Health to further the research which focuses on ways to inhibit CCR5, a protein that is the main chemokine receptor on the body’s immune cells, also known as T-cells. The grant will be awarded over a four-year period and builds upon a July 2014 study Sherman authored and published in Science Translational Medicine.
“It turns out that HIV and its evolution high-jacked that receptor and uses CCR5 as its primary way of binding to T-cells, entering them and killing them,” explains Sherman. “That’s what causes AIDS. CCR5 is not just present on T-cells but also exists in the liver on the surface of hepatocytes and also in the liver on stellate cells. Stellate cells are the cells that produce scar tissue in the liver which can lead to the development of cirrhosis. The focus of this grant is to look at how inhibition of CCR5 might influence the development of liver injury and/or the development of scar or cirrhosis in the liver.”
“An additional question to consider is, ‘How does interfering with CCR5 affect viruses like hepatitis C that might be co-infecting the liver?’” says Sherman. “We know hepatitis C causes liver injury, but is that injury modulated in part through this receptor, which may not be a specific receptor for hepatitis C but is for HIV?”
Medications have been developed to block the CCR5 receptor and Sherman will be examining their effect in clinical populations and conducting lab studies of the meds. Two medications that will be reviewed are Cenicriviroc, an investigational drug currently under study for the treatment of fatty liver, and Maraviroc which is currently approved for treatment of HIV.
Sherman says an aberrant CCR5 protein created by a CCR5-delta 32 gene mutation may be protecting individuals who have been exposed to HIV, but don’t have rapid AIDS progression. Researchers think CCR5-delta 32 mutation is a gene that was selected among Europeans as a result of another great epidemic, Europe’s black plague of the 14th century, explains Sherman.