BK virus large T and VP-1 expression in infected human renal allografts.
OBJECTIVE
We investigated the expression of early and late phase BK virus (BKV) proteins and their interactions with host cell proteins in renal allografts, with ongoing polyomavirus associated nephropathy (PVAN), and correlated this with the nuclear and cell morphology.


METHODS
Frozen sections from three patients with renal allografts (two biopsies, one explant) with PVAN were analysed by indirect immunofluorescence using BKV specific anti-polyoma large T-antigen and anti-VP-1 antibodies, as well as anti-p53, anti-Ki67, anti-caspase-3, anti-bcl2 and anti-cytokeratin 22 antibodies. Nuclear morphology and size were estimated by DNA Hoechst staining.


RESULTS
In infected tubular cells the early and late phases of infection could be distinguished according to expression of large T-antigen or VP-1. The early phase revealed almost normal nuclear proportions, whereas in later phases nuclear size increased about 2 to 3 fold. Expression of large T-antigen was strongly associated with accumulation of p53 in the nucleus, accompanied by the activation of the cell cycle associated cell protein Ki67. In contrast, expression of BKV VP1 correlated only weakly with p53. Virus dependent cell lysis was due to necrosis, since neither caspase 3 nor nuclear nor cytoskeleton changes indicated apoptosis.


CONCLUSIONS
In our selected patients with PVAN a clear distinction between early and late phases was possible, according to the protein expression patterns of BKV markers. Striking nuclear enlargement is only present in the late phase of infection. In the inflammatory setting of PVAN, BKV dependent effects appear to be mediated by the inhibition of p53, resulting in the activation of the cell cycle. We assume that in PVAN similar BKV mechanisms are operative as in certain in vitro systems.
Seemayer
Christian A
CA
Seemayer
Norbert H
NH
Dürmüller
Ursula
U
Gudat
Fred
F
Schaub
Stefan
S
Hirsch
Hans H
HH
Mihatsch
Michael J
MJ
D000328:Adult; D000368:Aged; D000957:Antigens, Viral, Tumor / Q000378:metabolism; D017209:Apoptosis; D001739:BK Virus / Q000472:pathogenicity* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007633:Keratins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology / Q000821:virology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000209:etiology* / Q000473:pathology / Q000821:virology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014412:Tumor Virus Infections / Q000209:etiology* / Q000473:pathology / Q000821:virology; D015678:Viral Structural Proteins / Q000378:metabolism
D000957:Antigens, Viral, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D015678:Viral Structural Proteins; D007633:Keratins; C505407:CASP3 protein, human; D053148:Caspase 3
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