title: High frequency, sustained T cell responses to PARV4 suggest viral persistence in vivo.
abstract: BACKGROUND
  Parvovirus 4 (PARV4) is a recently identified human virus that has been found in livers of patients infected with hepatitis C virus (HCV) and in bone marrow of individuals infected with human immunodeficiency virus (HIV). T cells are important in controlling viruses but may also contribute to disease pathogenesis. The interaction of PARV4 with the cellular immune system has not been described. Consequently, we investigated whether T cell responses to PARV4 could be detected in individuals exposed to blood-borne viruses.
  
  
  METHODS
  Interferon γ (IFN-γ) enzyme-linked immunospot assay, intracellular cytokine staining, and a tetrameric HLA-A*0201-peptide complex were used to define the lymphocyte populations responding to PARV4 NS peptides in 88 HCV-positive and 13 HIV-positive individuals. Antibody responses were tested using a recently developed PARV4 enzyme-linked immunosorbent assay.
  
  
  RESULTS
  High-frequency T cell responses against multiple PARV4 NS peptides and antibodies were observed in 26% of individuals. Typical responses to the NS pools were >1000 spot-forming units per million peripheral blood mononuclear cells.
  
  
  CONCLUSIONS
  PARV4 infection is common in individuals exposed to blood-borne viruses and elicits strong T cell responses, a feature typically associated with persistent, contained infections such as cytomegalovirus. Persistence of PARV4 viral antigen in tissue in HCV-positive and HIV-positive individuals and/or the associated activated antiviral T cell response may contribute to disease pathogenesis.
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Simmons
authors.forename: Colin
authors.initials: C
authors.lastname: Sharp
authors.forename: Stuart
authors.initials: S
authors.lastname: Sims
authors.forename: Henrik
authors.initials: H
authors.lastname: Kloverpris
authors.forename: Philip
authors.initials: P
authors.lastname: Goulder
authors.forename: Peter
authors.initials: P
authors.lastname: Simmonds
authors.forename: Paul
authors.initials: P
authors.lastname: Bowness
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000276:immunology; D006526:Hepatitis C / Q000150:complications / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D010322:Parvoviridae Infections / Q000276:immunology*; D017992:Parvovirus / Q000145:classification* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma