Since the third base in this situation is of no consequence for defining the encoded amino acid, it would be anticipated that, over time, random mutations would result in the given amino acid being encoded by any of four sequences, with the same bases in positions 1 and 2, and A, T, G, or C in position 3. This variability in position 3 would have no effect on the amino acid sequence of the encoded polypeptide. However, if there were an overlapping reading frame, an insignificant change in base position 3 in one reading frame could produce a significant alteration in the amino acid composition of a polypeptide encoded in an overlapping, alternative reading frame. Based on these theoretical considerations, diverse HCV sequences were obtained from GenBank and aligned. Analysis of sera from patients with chronic HCV has demonstrated that an appreciable proportion of them contain antibodies to the A-ORF protein, indicating that the protein must be synthesized during chronic HCV infection.
Efforts are now ongoing to identify the protein itself in liver samples from infected patients.
The identified protein may be of value in improved HCV diagnostics. Moreover, the new protein, as well as the uniquely conserved region of the HCV genome that encodes it, are potential targets for a variety of new anti-HCV therapeutic strategies. It is likely that therapies developed on the basis of these observations will eventually undergo clinical evaluation within our program at Mount Sinai. Mechanisms, diagnosis and treatment of hepatic fibrosis Dr. Scott Friedman was the first to isolate and characterize the hepatic stellate cell, which is the key cell type responsible for scar production in liver. This work has led to major advances in our understanding of how the liver responds to injury and points the way towards new treatments.