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Clinical and Vaccine Immunology, August 2007, p. 959-968, Vol. 14, No. 8
1071-412X/07/$08.00+0     doi:10.1128/CVI.00123-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Human Polyomavirus Type 1 (BK Virus) Agnoprotein Is Abundantly Expressed but Immunologically Ignored

David Leuenberger,^1, Per Arne Andresen,² Rainer Gosert,¹ Simone Binggeli,¹ Erik H. Ström,² Sohrab Bodaghi,¹ Christine Hanssen Rinaldo,³ and Hans H. Hirsch^1,4*

Transplantation Virology, Institute for Medical Microbiology, Department of Clinical and Biological Sciences, University of Basel, Basel, Switzerland,¹ Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway,² Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway,³ Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland⁴

Received 17 March 2007/ Returned for modification 17 May 2007/ Accepted 21 May 2007

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.

Published ahead of print on 30 May 2007.

Present address: Department of Internal Medicine, Kantonsspital Aarau, Aarau, Switzerland.

This article has been cited by other articles:

• Gosert, R., Rinaldo, C. H., Funk, G. A., Egli, A., Ramos, E., Drachenberg, C. B., Hirsch, H. H. (2008). Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology. J. Exp. Med. 205: 841-852 [Abstract] [Full Text]  
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