HUMORAL IMMUNE-RESPONSE TO THE E2 PROTEIN OF HEPATITIS-G VIRUS IS ASSOCIATED WITH LONG-TERM RECOVERY FROM INFECTION AND REVEALS A HIGH-FREQUENCY OF HEPATITIS-G VIRUS EXPOSURE AMONG HEALTHY BLOOD-DONORS

The second envelope protein (E2) of the hepatitis G virus (HGV) was ex pressed in Chinese hamster ovary (CHO) cells and showed a molecular we ight of approximately 60 to 70 kd, with 15 to 25 kd of the size contri buted by N-linked glycosylation. An enzyme-linked immunosorbent assay (ELISA) using HGV-E2 was developed to test for antibodies to this prot ein (anti-E2) in human sera. High sensitivity was achieved by developi ng monoclonal antibodies (mAbs) to HGV-EZ, which were used as capture antibodies in the ELISA. Our studies revealed that 16% of healthy Span ish blood donors were exposed to HGV, indicating that additional route s of viral transmission besides parenteral exposure might exist. An ev en higher prevalence of exposure to HGV (52%-73%) was found in several groups at risk of parenteral exposure to infectious agents, i.e., int ravenous drug users, transfusion history, hemophiliacs, and hepatitis C virus (HCV)-positive patients. Most anti-E2-positive patients were H GV-RNA-negative and vice versa, indicating an !inverse correlation of these two viral markers. A panel of 16 posttransfusion patients follow ed for up to 16 years revealed that patients who develop an anti-E2 re sponse become HGV-RNA-negative, while patients who do not develop anti -E2 are persistently infected. Immunity to HGV seems to be long-lastin g, because circulating antibody to E2 could still be detected 14 years after seroconversion. Sequence comparisons showed that E2 is highly c onserved among isolates collected worldwide, indicating that immune es cape variants are not common in HGV infections. This reflects on a mol ecular level why HGV infections usually are cleared spontaneously by t he host. However, possible mechanisms of HGV persistence, as found in some patients, remain to be elucidated.