title: Human polyomavirus type 1 (BK virus) agnoprotein is abundantly expressed but immunologically ignored.
abstract: Impaired BK virus (BKV)-specific immunity is a key risk factor of polyomavirus-associated nephropathy. We hypothesized that BKV agnoprotein might constitute an important immune target, as it is highly expressed after infection in vitro. We demonstrate abundant expression of BKV agnoprotein in vivo by immunostaining of kidney transplant (KT) biopsy specimens. Antibody responses to the recombinant affinity-purified BKV agnoprotein, large tumor (LT), and VP1 antigens in 146 sera from 38 KT patients and in 19 sera from 16 healthy donors (HD) were compared by enzyme immunoassay. In HD, low titers of anti-agnoprotein immunoglobulin G (IgG) were found in 15% of sera, compared to 41% for anti-LT antigen and 63% for anti-VP1. No anti-BKV IgM was detectable. In KT patients, anti-agnoprotein IgG and IgM were found in 8% and 3.6% of sera, compared to 63% and 18% for anti-LT IgG and IgM and 80% and 41% for anti-VP1 IgG and IgM, respectively. Anti-LT antigen and anti-VP1, but not anti-agnoprotein, activities increased during and after BKV viremia in KT patients. To investigate specific cellular immune responses, we compared levels of gamma interferon production in peripheral blood mononuclear cells (PBMC) of 10 HD and 30 KT patients by enzyme-linked immunospot assay. In HD, the median numbers of gamma interferon spot-forming units per million PBMC for the agnoprotein, LT antigen, and VP1 peptides were 1, 23, and 25, respectively, whereas the responses in KT patients were 2, 24, and 99, respectively. We conclude that BKV agnoprotein, though abundantly expressed in vivo, is poorly recognized immunologically.
authors.affiliation: Transplantation Virology, Institute for Medical Microbiology, Department of Clinical and Biological Sciences, University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Leuenberger
authors.forename: Per Arne
authors.initials: PA
authors.lastname: Andresen
authors.forename: Rainer
authors.initials: R
authors.lastname: Gosert
authors.forename: Simone
authors.initials: S
authors.lastname: Binggeli
authors.forename: Erik H
authors.initials: EH
authors.lastname: Ström
authors.forename: Sohrab
authors.initials: S
authors.lastname: Bodaghi
authors.forename: Christine Hanssen
authors.initials: CH
authors.lastname: Rinaldo
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D000957:Antigens, Viral, Tumor / Q000276:immunology; D001739:BK Virus / Q000276:immunology*; D001706:Biopsy; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D007674:Kidney Diseases / Q000276:immunology* / Q000821:virology; D016030:Kidney Transplantation / Q000276:immunology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D027601:Polyomavirus Infections / Q000276:immunology / Q000821:virology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication; D000086082:Viroporin Proteins
chemical_list: D000914:Antibodies, Viral; D000957:Antigens, Viral, Tumor; D007371:Interferon-gamma; D011994:Recombinant Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins