Seroprevalence of GB virus C and persistence of RNA and antibody

Abstract

Exposure to GB virus C (GBV-C) was determined in several U.S. populations by both reverse-transcription-polymerase chain reaction (RT-PCR) and by an enzyme linked immunosorbent assay (ELISA) for antibodies to mammalian cell-expressed GBV-C envelope protein, E2 (GBV-C E2). Most individuals exposed to GBV-C were either RNA positive/ELISA negative or ELISA positive/RNA negative. Exposure, therefore, was measured as the sum of GBV-C RNA positive and GBV-C E2 antibody positive specimens, and was higher in commercial plasmapheresis donors (40.5%) than in volunteer blood donors (5.5%). In intravenous drug users (IVDUs), GBV-C exposure was 89.2%. Serial bleed specimens tested for GBV-C RNA indicate that some patients remain viremic for at least 3 years and fail to produce detectable antibodies to GBV-C E2. In other exposed individuals who tested negative for GBV-C RNA, antibodies to E2 appear to be similarly long-lived (greater than 3 years) with a fairly constant titer (ranging in reciprocal endpoint dilution from 336 to 21,504). Since the detection of GBV-C RNA and GBV-C E2 antibody are mutually exclusive in most exposed individuals, studies pertaining to incidence and prevalence of GBV-C infection require both antibody and nucleic acid detection.

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

“…Some recent reports describe the detection of anti-HPgV peptide antibodies (Fernández et al, 2013;Gó mara et al, 2011); however, no clear relationship between peptide-reactive antibodies in actively HPgV-infected or convalescent subjects has been reported. As anti-E2 antibody is usually inversely related to HPgV viraemia (Gutierrez et al, 1997;Tacke et al, 1997;Tanaka et al, 1998a), it is possible that HPgV suppresses the production of antibodies, contributing to persistent infection. There are some data suggesting that HPgV may reduce B-cell activation in addition to T-cell activation.…”

“…As noted above, antibodies against HPgV structural proteins are generally not detected during viraemia and most individuals develop conformation-dependent antibodies to E2 at or shortly following viral clearance (Gutierrez et al, 1997;Tacke et al, 1997;Tanaka et al, 1998a). However, anti-E2 antibodies are occasionally found during active viraemia and some of these individuals may be in the act of clearing viraemia (Schwarze-Zander et al, 2006;Tan et al, 1999;Williams et al, 2004).…”

“…Although HPgV is not as efficient at establishing persistent infection as HCV, an estimated 25 % of infections persist and the other 75 % clear viraemia within 2 years of infection (Gutierrez et al, 1997;Tanaka et al, 1998a). The prevalence of HPgV viraemia in cross-sectional serum surveys of healthy blood donors in developed countries is between 1 and 5 %, whilst up to 20 % of blood donors in developing countries have active infection (Mohr & Stapleton, 2009).…”

“…Based on cross-sectional prevalence data, there are~750 million people with HPgV viraemia worldwide (Stapleton et al, 2014). Anti-HPgV antibodies are not usually detected during active infection, but antibody against the envelope glycoprotein E2 appears following viral clearance (Gutierrez et al, 1997;Tacke et al, 1997;Tanaka et al, 1998a;Thomas et al, 1997). These E2 antibodies appear to provide partial protection against reinfection (Elkayam et al, 1999;Tillmann et al, 1998).…”

“…These E2 antibodies appear to provide partial protection against reinfection (Elkayam et al, 1999;Tillmann et al, 1998). Thus, antibody to E2 represents a marker of prior infection, although antibody levels may decrease and become undetectable over time (Gutierrez et al, 1997;Tacke et al, 1997;Tanaka et al, 1998a). As 12-20 % of blood donors from developed countries have HPgV E2 antibodies (Gutierrez et al, 1997;Tacke et al, 1997) and a higher percentage of healthy blood donors in developing countries have E2 antibodies (reviewed by Mohr & Stapleton, 2009), the data suggest that~1.5-2.5 billion people are currently infected or have evidence of prior HPgV infection, making this virus a major contributor to the human virome.…”