title: Human Pegivirus (HPgV; formerly known as GBV-C) inhibits IL-12 dependent natural killer cell function.
abstract: Human Pegivirus (HPgV, formally GB virus C) infects lymphocytes and NK cells in vivo, and infection is associated with reduced T cell and NK cell activation in HIV-infected individuals. The mechanism by which HPgV inhibits NK cell activation has not been assessed. Following IL-12 stimulation, IFNγ expression was lower in HIV-HPgV co-infected subjects compared to HIV mono-infected subjects (p=0.02). In addition, HPgV positive human sera, extracellular vesicles containing E2 protein, recombinant E2 protein and synthetic E2 peptides containing a predicted Tyk2 interacting motif inhibited NK cell IL-12-mediated IFNγ release. E2 protein also inhibited Tyk2 activation following IL-12 stimulation. In contrast, cytolytic NK cell function was not altered by HPgV. Inhibition of NK cell-induced proinflammatory/antiviral cytokines may contribute to both HPgV persistence and reduced immune activation during HIV-coinfection. Understanding mechanisms by which HPgV alters immune activation may contribute towards novel immunomodulatory therapies to treat HIV and inflammatory diseases.
authors.affiliation: The Iowa City Veterans Affairs Medical Center The University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary program in Molecular and Cellular Biology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Ernest T
authors.initials: ET
authors.lastname: Chivero
authors.affiliation: The Iowa City Veterans Affairs Medical Center The University of Iowa, Iowa City, IA 52242, USA; Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Nirjal
authors.initials: N
authors.lastname: Bhattarai
authors.affiliation: The Iowa City Veterans Affairs Medical Center The University of Iowa, Iowa City, IA 52242, USA; Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: McLinden
authors.affiliation: The Iowa City Veterans Affairs Medical Center The University of Iowa, Iowa City, IA 52242, USA; Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xiang
authors.affiliation: The Iowa City Veterans Affairs Medical Center The University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary program in Molecular and Cellular Biology, The University of Iowa, Iowa City, IA 52242, USA; Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA; Department of Microbiology, The University of Iowa, Iowa City, IA 52242, USA. Electronic address: jack-stapleton@uiowa.edu.
authors.forename: Jack T
authors.initials: JT
authors.lastname: Stapleton
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D060085:Coinfection; D005260:Female; D018178:Flaviviridae Infections / Q000276:immunology / Q000473:pathology / Q000821:virology*; D005416:Flavivirus / Q000472:pathogenicity / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007371:Interferon-gamma; D018664:Interleukin-12 / Q000494:pharmacology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
chemical_list: D014759:Viral Envelope Proteins; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: GBV-C; HPgV; Immune modulation; NK cells; Tyk2