Hepatitis C virus E2-CD81 interaction induces hypermutation of the immunoglobulin gene in B cells.

ABSTRACT: Hepatitis C virus (HCV) is one of the leading causes of chronic liver diseases and B-lymphocyte proliferative disorders, including mixed cryoglobulinemia and B-cell lymphoma. It has been suggested that HCV infects human cells through the interaction of its envelope glycoprotein E2 with a tetraspanin molecule CD81, the putative viral receptor. Here, we show that the engagement of B cells by purified E2 induced double-strand DNA breaks specifically in the variable region of immunoglobulin (V(H)) gene locus, leading to hypermutation in the V(H) genes of B cells. Other gene loci were not affected. Preincubation with the anti-CD81 monoclonal antibody blocked this effect. E2-CD81 interaction on B cells triggered the enhanced expression of activation-induced cytidine deaminase (AID) and also stim

SUBMITTER: Machida K 

PROVIDER: S-EPMC1143751 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature