Hepatitis C Virus Core Protein Discriminates Between the Two IgG2 Allotypes

Abstract

Immunoglobulin GM allotypes, genetic markers of IgG, are associated with the outcome of hepatitis C virus (HCV) infection, but the underlying mechanisms are not completely understood. HCV has evolved mechanisms for decreasing the efficacy of the host immune response. One such strategy might involve the scavenging of the Fcγ domain of the anti-HCV IgG antibodies by its Fcγ-receptor–like core protein and thus interfering with the Fcγ-mediated host defense mechanisms. We tested the hypothesis that GM allotypes modulate this viral strategy through differential binding to the core protein. Here we show that the absorbance values for binding to the core protein were higher for GM23+IgG2 than for GM23−IgG2 (p = 0.027), a finding that at least in part explains the involvement of GM allotypes in the outcome of HCV infection. These findings also contribute toward our understanding of the mechanisms that maintain strong linkage disequilibrium between particular GM alleles.