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A novel blood-borne human pegivirus (HPgV), HPgV-2, was recently identified in hepatitis C virus (HCV)-infected individuals and individuals who had received multiple transfusions. Robust serological assays capable of detecting antibodies in HPgV-2-infected individuals are needed to establish global seroprevalence rates and potential disease associations. The two objectives of this study were to determine the utility of mammalian cell-expressed HPgV-2 E2 glycoprotein or bacterium-expressed nonstructural protein 4AB (NS4AB) in detecting past or present infections and to compare the total prevalence (antibody and RNA positive) of HPgV-2 with that of the other human pegivirus, HPgV-1 (GB virus C [GBV-C]). HPgV-2 E2 antibodies were detected in 13 (92.86%) of 14 HPgV-2-viremic cases, and NS4AB antibodies were detected in 8 (57.14%) of 14 cases. The HPgV-2 seroprevalence was significantly higher (P &lt; 0.0001) among HCV-infected individuals (3.31% [24 of 726 samples]) than among non-HCV-infected individuals (0.30% [4 of 1,348 samples]). Of 31 anti-E2-positive samples, 22 had supplemental supporting data; 12 samples were HPgV-2 RNA positive and 10 nonviremic samples were antibody positive for peptides or NS4AB. The total prevalence of HPgV-1 (35.00%) was significantly higher than that of HPgV-2 (1.33%) in all populations tested (P &lt; 0.0001). For HPgV-1, codetection of antibodies to E2 and RNA was infrequent (5.88%). In contrast, antibodies to E2 were detected in most HPgV-2-viremic individuals (92.86%), as is observed among individuals chronically infected with HCV, most of whom are antibody positive for HCV E2. Our studies indicate that HPgV-2 circulates with HCV and displays a profile similar to the serological profile of HCV-infected persons, although the pathogenicity of this virus has yet to be established.

Antibodies to the Novel Human Pegivirus 2 Are Associated with Active and Resolved Infections