The hepatitis C virus hijacks the body's immune system, leaving T cells unable to function. A new study in animal models suggests that blocking a protein that helps the virus thrive could restore immune function, allowing the body to fight infection. The work, led by teams at The Research Institute at Nationwide Children's Hospital and Emory University, was published online Aug. 26 in the Proceedings of the National Academy of Sciences.
Previous studies show that antibody treatments that inhibit the protein, called programmed cell death 1 (PD-1), can shrink tumors in humans. This new work suggests that anti-PD-1 antibodies might be equally effective in treating hepatitis C and other persistent human viral infections, says Christopher Walker, PhD, a senior author on the study and director of the Center for Vaccines and Immunity at Nationwide Children's.
PD-1 is a regulatory protein that helps keep the immune system in check. Normally, PD-1 acts as a switch to turn off immune responses when an infection is under control. Some viruses such as HCV manipulate the PD-1 off switch so that T cells lose their ability to fight the infection, a condition scientists call "T-cell exhaustion." The result is life-long persistence of HCV in the liver, which increases the risk of cirrhosis, liver cancer and other serious diseases.
The researchers treated animal models with persistent HCV infection with repeated doses of an anti-PD-1 antibody. Although the responses were mixed, one animal did show a dramatic increase in HCV-specific T cell activity in the liver and a sharp decrease in viral load. A closer examination of the data found that the animal had more HCV-specific T cells in the liver before therapy, which could mean that therapeutic success hinges on the amount of HCV-specific T cells in the liver before treatment.
