A recent letter in Nature Medicine has shed some more light on Hepatitis C virus’ impact on the immune system of compromised individuals. The research team, led by Abigail Jarret, a graduate student at Yale University, reported that two microRNAs, miR-208b and miR-499a-5p, which are overexpressed in infected hepatocytes, weaken immune response through downregulating IFNAR1 (a type I interferon receptor) expression. Previous studies have shown that miR-208b and miR-499a-5p also suppress expression of IFNL2 and IFNL3, both type III interferons, thus increasing HCV persistence.
This work helps to explain why current interferon-alpha and ribavirin therapies are not as effective as researchers would hope. We now know that HCV impacts the immune response in two ways – by halting type III interferon assembly, and by preventing production of the receptors type I interferons need to properly function. According to Jarret, since these therapies utilize type I interferon, HCV may be able to persist by simply inactivating type III interferons, explaining why treatment fails for nearly 60% of patients.