Research Focuses on CCR5 Inhibition and Liver Injury

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.

Inhibiting the chemokine receptor CCR5 to prevent liver injury and cirrhosis is going to be the focus of research at the University of Cincinnati. 

The research will be funded by a $2 million grant from the National Institutes of Health, and builds upon an earlier study published by Kenneth Sherman, MD, PhD, professor of digestive diseases at the University of Cincinnati and colleagues in Science Translational Medicine.1

“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,” Dr Sherman noted in a prepared statement about the research. “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.”

Dr Sherman and colleagues will be examining the investigational medication cenicriviroc, as well as maraviroc and their effects in clinical populations. 

Dr Sherman explained that 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.

“HIV has been particularly devastating in Africa. It is certainly a terrible disease in Europe and the United States. but some people had slower disease progression.” Sherman noted in the statement. “Those that didn’t get high HIV viral loads and had slow AIDS progression were called ‘elite controllers.'” 

“Research showed that Europeans and people of European descent who were selected genetically through their ancestors during the plague—the black death of Europe — and they have the CCR5-delta 32 mutation,” Dr Sherman said. His research will focus on patients with hemophilia who were enrolled in the long-term longitudinal cohort called the Multicenter Hemophilia Cohort Study. 


1. Sherman K, Guedj J, Tarek Shata M, et al. Modulation of HCV replication after combination antiretroviral therapy in HCV/HIV co-infected patients. Sci Translat Med. 2014; DOI: 10.1126/scitranslmed.3008195.