Antibodies to the novel human Pegivirus, HPgV-2, are associated with active and resolved infection.

A novel human blood borne Pegivirus, HPgV-2, was recently identified in HCV-infected and multiply transfused individuals. Robust serologic assays capable of detecting antibodies in HPgV-2 infected individuals are needed to establish global seroprevalence and potential disease association. The two objectives of this study are to determine the utility of mammalian-expressed HPgV-2 E2 glycoprotein or bacteria-expressed NS4AB in detecting past or present infection, and to compare the total prevalence (antibody and RNA positive) of HPgV-2 to the other human pegivirus, HPgV-1 (GBV-C). HPgV-2 E2 antibodies were detected in 13 of 14 (92.86%) HPgV-2 viremic cases, and NS4AB antibodies were detected in 8 of 14 (57.14%) cases. The HPgV-2 seroprevalence (3.31%, 24 of 726 samples) was significantly higher (p<0.0001) in HCV infected individuals than in non-HCV infected individuals (0.30%, 4 of 1348 samples). Among 31 anti-E2 positive samples, 22 had supplemental supporting data: 12 were HPgV-2 RNA positive and 10 non-viremic samples were antibody positive for peptides or NS4AB. Total prevalence of HPgV-1 (35.00%) was significantly higher than HPgV-2 (1.33%) in all populations tested (p<0.0001). For HPgV-1, co-detection of antibodies to E2 and RNA was infrequent (5.88%). In contrast, antibodies to E2 are detected in most HPgV-2 viremic individuals (92.86%), as is observed among individuals chronically infected with HCV where most are antibody positive for HCV E2. Our studies indicate that HPgV-2 circulates with HCV and displays similarities to the serologic profile of HCV infected persons, although the pathogenicity of this virus has yet to be established.