Antigenic relevance of F protein in chronic hepatitis C virus infection

The hepatitis C virus (HCV) F protein is a recently described, frameshift product of HCV core encoding sequence of genotype 1a. Its function and antigenic properties are unknown. Using enzyme‐linked immunosorbent assay, we assessed the prevalence of anti‐F antibodies in 154 patients chronically infected with HCV, 65 patients with other liver diseases, and 121 healthy controls. For this purpose, we expressed a highly purified HCV F recombinant protein from HCV genotype 1a in Escherichia coli. Because the F protein shares the 10 first amino acids with the core protein, the anti‐HCV F response was also assessed by a F recombinant protein deleted of its 10 first amino acids [Δ(1‐10)‐F]. Ninety‐six (62%) of the 154 HCV serum samples reacted with the complete F recombinant protein, whereas 39 (25%) showed a weaker anti‐Δ(1‐10)F reactivity and 150 (97%) had anti‐core antibodies. No reactivity against F, Δ(1‐10)F, or core was detected in any of the controls. To exclude a potential cross‐reaction of anti‐F antibodies with anti‐core antibodies, a specific enzyme‐linked immunosorbent assay was performed for anti‐core antibodies. The specificity of anti‐F antibodies was confirmed using an F synthetic peptide. The prevalence of anti‐F antibodies did not correlate with HCV RNA serum level, genotype, or stage of liver disease. Sequence analysis from 8 anti‐F–‐positive and 5 anti‐F–‐negative serum samples did not reveal any particular difference potentially accounting for their respective anti‐F responses. In conclusion, the F protein elicits specific antibodies in 62% of individuals chronically infected with HCV; such anti‐F response does not seem to be affected by the F sequence heterogeneity. (Hepatology 2004;40:900‐909).