title: Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection.
abstract: Hepatitis C virus (HCV) and human pegivirus (HPgV), formerly GBV-C, are the only known human viruses in the Hepacivirus and Pegivirus genera, respectively, of the family Flaviviridae. We present the discovery of a second pegivirus, provisionally designated human pegivirus 2 (HPgV-2), by next-generation sequencing of plasma from an HCV-infected patient with multiple bloodborne exposures who died from sepsis of unknown etiology. HPgV-2 is highly divergent, situated on a deep phylogenetic branch in a clade that includes rodent and bat pegiviruses, with which it shares <32% amino acid identity. Molecular and serological tools were developed and validated for high-throughput screening of plasma samples, and a panel of 3 independent serological markers strongly correlated antibody responses with viral RNA positivity (99.9% negative predictive value). Discovery of 11 additional RNA-positive samples from a total of 2440 screened (0.45%) revealed 93-94% nucleotide identity between HPgV-2 strains. All 12 HPgV-2 RNA-positive cases were identified in individuals also testing positive for HCV RNA (12 of 983; 1.22%), including 2 samples co-infected with HIV, but HPgV-2 RNA was not detected in non-HCV-infected individuals (p<0.0001), including those singly infected by HIV (p = 0.0075) or HBV (p = 0.0077), nor in volunteer blood donors (p = 0.0082). Nine of the 12 (75%) HPgV-2 RNA positive samples were reactive for antibodies to viral serologic markers, whereas only 28 of 2,429 (1.15%) HPgV-2 RNA negative samples were seropositive. Longitudinal sampling in two individuals revealed that active HPgV-2 infection can persist in blood for at least 7 weeks, despite the presence of virus-specific antibodies. One individual harboring both HPgV-2 and HCV RNA was found to be seronegative for both viruses, suggesting a high likelihood of simultaneous acquisition of HCV and HPgV-2 infection from an acute co-transmission event. Taken together, our results indicate that HPgV-2 is a novel bloodborne infectious virus of humans and likely transmitted via the parenteral route.
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois, United States of America.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Berg
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, California, United States of America.|UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, California, United States of America.
authors.forename: Deanna
authors.initials: D
authors.lastname: Lee
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois, United States of America.
authors.forename: Kelly
authors.initials: K
authors.lastname: Coller
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Frankel
authors.affiliation: Center for Liver Diseases, University of Chicago Medical Center, Chicago, Illinois, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Aronsohn
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois, United States of America.
authors.forename: Kevin
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois, United States of America.
authors.forename: Kenn
authors.initials: K
authors.lastname: Forberg
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois, United States of America.
authors.forename: Marilee
authors.initials: M
authors.lastname: Marcinkus
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, California, United States of America.|UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, California, United States of America.
authors.forename: Samia N
authors.initials: SN
authors.lastname: Naccache
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois, United States of America.
authors.forename: George
authors.initials: G
authors.lastname: Dawson
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois, United States of America.
authors.forename: Catherine
authors.initials: C
authors.lastname: Brennan
authors.affiliation: Center for Liver Diseases, University of Chicago Medical Center, Chicago, Illinois, United States of America.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Jensen
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Hackett
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, California, United States of America.|UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, California, United States of America.|Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, California, United States of America.
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Chiu
mesh_terms: D001483:Base Sequence; D060085:Coinfection / Q000235:genetics / Q000821:virology; D005260:Female; D018178:Flaviviridae Infections / Q000235:genetics / Q000821:virology*; D029407:GB virus C / Q000235:genetics*; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000235:genetics / Q000821:virology*; D006525:Hepatitis, Viral, Human / Q000235:genetics / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction