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

✍ Scribed by M Tacke; S Schmolke; V Schlueter; S Sauleda; J I Esteban; E Tanaka; K Kiyosawa; H J Alter; U Schmitt; G Hess; B Ofenloch-Haehnle; A M Engel

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 300 KB
• Volume: 26
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510260635

✦ Synopsis

The second envelope protein (E2) of the hepatitis G virus patients, remain to be elucidated. (HEPATOLOGY 1997;26: 1626-1633.) (HGV) was expressed in Chinese hamster ovary (CHO) cells and showed a molecular weight of approximately 60 to 70 kd, with 15 to 25 kd of the size contributed by N-linked

Recently, two groups independently reported on the clonglycosylation. An enzyme-linked immunosorbent assay ing and sequencing of a novel flavivirus-like agent, desig-(ELISA) using HGV-E2 was developed to test for antibodies nated hepatitis G virus (HGV) 1 or GB virus-C. 2,3 Sequence to this protein (anti-E2) in human sera. High sensitivity was comparisons of these viruses suggested that they are different achieved by developing monoclonal antibodies (mAbs) to isolates of the same virus (subsequently referred to as HGV). HGV-E2, which were used as capture antibodies in the ELISA.

The genomic organization of HGV was reported to be similar Our studies revealed that 16% of healthy Spanish blood doto hepatitis C virus (HCV), with about 25% sequence homolnors were exposed to HGV, indicating that additional routes ogy at the amino acid level. HGV is an enveloped, singleof viral transmission besides parenteral exposure might exist.

stranded RNA virus with a genome of approximately 9,400 An even higher prevalence of exposure to HGV (52%-73%) nucleotides containing a continuous open reading frame prewas found in several groups at risk of parenteral exposure dicted to encode a polyprotein of 2,873 amino acids; the to infectious agents, i.e., intravenous drug users, transfusion latter is putatively cleaved by host and viral proteases, rehistory, hemophiliacs, and hepatitis C virus (HCV)-positive sulting in several structural and nonstructural proteins. 1 patients. Most anti-E2-positive patients were HGV-RNA-HGV contains several sequence motifs that are common negative and vice versa, indicating an inverse correlation of among the members of the flaviviridae. However, the isolates these two viral markers. A panel of 16 posttransfusion pacharacterized so far lack an intact core protein. 1-4 tients followed for up to 16 years revealed that patients who A HGV-RNA prevalence of 0.9% to 3% has been reported develop an anti-E2 response become HGV-RNA-negative, among healthy blood donors. 1,5,6 Prevalence in populations while patients who do not develop anti-E2 are persistently at risk for parenteral exposure to infectious agents was much infected. Immunity to HGV seems to be long-lasting, because higher; more than 30% of intravenous drug users have been circulating antibody to E2 could still be detected 14 years found to be positive for HGV RNA. 7 The parenteral route after seroconversion. Sequence comparisons showed that E2 of transmission of HGV has also been shown in multiple is highly conserved among isolates collected worldwide, inditransfused individuals. 1 However, the course of infection, site cating that immune escape variants are not common in HGV of replication, and clinical significance of infection with HGV infections. This reflects on a molecular level why HGV infecstill remain largely unresolved. tions usually are cleared spontaneously by the host. However, Until recently, diagnosis of HGV infections was restricted possible mechanisms of HGV persistence, as found in some to reverse-transcriptase polymerase chain reaction detection of viral RNA. However, specific immunoassays for the detection of HGV are needed to investigate the immune response Abbreviations: HGV, hepatitis G virus; HCV, hepatitis C virus; E2, second envelope and course of infection and to estimate the prevalence of protein; ELISA, enzyme-linked immunosorbent assay; anti-E2, antibody to hepatitis G HGV infections in the population, because antibodies to the virus second envelope protein; mAbs, monoclonal antibodies; Mc5, HGV-E2-specific monoclonal antibody M clone5; CHO, Chinese hamster ovary; SDS-PAGE, sodium virus are likely to be still present after spontaneous clearance dodecyl sulfate-polyacrylamide gel electrophoresis; PNGase F, N-glycosidase F.

of the virus.