A researcher from the University of Cincinnati is using genetic information from a disease that killed thousands of Europeans in the 14th century as a tool to possibly develop treatments for HIV patients who are also infected with hepatitis C and are using antiretroviral regimens.
Kenneth Sherman, Gould professor of medicine, has been using genetic clues left behind by Europe's infamous Black Death to accomplish his goal. This begins with studying blood samples from thousands of patients who came in contact with the HIV virus throughout the 1980s and 1990s in an effort to determine if an inherited genetic variant that has been shown to be effective against HIV could also benefit patients living with hepatitis C and other diseases of the liver.
Sherman's studies will also focus on inhibiting CCR5, a main receptor in the immune system. The new studies are a continuation of a study Sherman conducted in 2014. He will fund his research with a four-year, $2 million grant from the National Institutes of Health (NIH).
"It turns out that HIV and its evolution hijacked that receptor and uses CCR5 as its primary way of binding to T-cells, entering them and killing them," Sherman said. "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 the development of scar or cirrhosis in the liver."
Sherman will also study how CCR5 interference might affect viruses like hepatitis C that attack the liver.
"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?" he said.
Sherman's study will also test CCR5-blocking medications that have already been developed or marketed, including Cenicriviroc and Maraviroc, in clinical and lab settings.
"HIV has been particularly devastating in Africa," Sherman said. "It is certainly a terrible disease in Europe and the U.S., but some people had slower disease progression. Those that didn't get high HIV viral loads and had slow AIDS progression were called 'elite controllers.'"
Black Death is believed to have been rooted in a CCR5-delta 32 mutation gene.
"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," Sherman said. "If, over the next few years, we can show that CCR5 blockade protects HIV-infected people from liver disease, then we may change the entire treatment paradigm of HIV and make this part of the routine treatment of many or most patients."
