After analyzing the genetic changes in the sites, called epitopes, where the T cells specifically bind to the virus, the researchers found no changes had occurred during the one year of follow-up in the one patient who self-recovered. However, in the remaining seven patients, there were changes in 69 percent of T-cell epitopes, showing that the virus had mutated at key locations necessary for chronic infection to proceed.
Additional analysis showed that changes in T-cell epitopes were 13 times more frequent than changes in the remaining genome of the virus. The researchers examined the binding ability of T cells obtained early in infection to recognize 10 viral peptides known to have changed during the first six months of infection. Eight showed severely reduced capacity to stimulate production of interferon gamma, offering confirmation that the virus was mutating to evade the immune system.
Analysis of the viral RNA in the blood of seven patients with chronic infections revealed that eight of 16 changes in genome matched to the consensus sequence, confirming the presence of selective evolutionary pressure toward restoration of an ancestral form of the virus.
In the second study, using blood samples collected in Cork, Ireland, the researchers compared the genetic makeup of the virus in 22 chronically infected women to the original strain that had infected them more than 20 years before. The women were among hundreds accidentally infected in 1977 by a blood product tainted with hepatitis C, providing the researchers with unique access to the source of the infection, which came from a single donor unaware of having the illness.
Using computer analysis techniques developed at Hopkins, the scientists mapped these changes against the genetic makeup of the women's immune response. The researchers found th
Contact: David March
Johns Hopkins Medical Institutions