Abstract
BackgroundThe human polyomavirus BK (BKV) infects humans worldwide and establishes a persistent infection in the kidney. The BK virus genome encodes three regulatory proteins, large and small tumor-antigen and the agnoprotein, as well as the capsid proteins VP1 to VP3. Agnoprotein is conserved among BKV, JC virus (JCV) and SV40, and agnoprotein-deficient mutants reveal reduced viral propagation. Studies with JCV and SV40 indicate that their agnoproteins may be involved in transcription, replication and/or nuclear and cellular release of the virus. However, the exact function(s) of agnoprotein of BK virus remains elusive.Principal FindingsAs a strategy of exploring the functions of BKV agnoprotein, we decided to look for cellular interaction partners for the viral protein. Several partners were identified by yeast two-hybrid assay, among them α-SNAP which is involved in disassembly of vesicles during secretion. BKV agnoprotein and α-SNAP were found to partially co-localize in cells, and a complex consisting of agnoprotein and α-SNAP could be co-immunoprecipitated from cells ectopically expressing the proteins as well as from BKV-transfected cells. The N-terminal part of the agnoprotein was sufficient for the interaction with α-SNAP. Finally, we could show that BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter suggesting that agnoprotein may modulate exocytosis.ConclusionsWe have identified the first cellular interaction partner for BKV agnoprotein. The most N-terminal part of BKV agnoprotein is involved in the interaction with α-SNAP. Presence of BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter.
Highlights
Polyomaviridae are non-enveloped viruses containing a circular double stranded DNA genome of approximately 5,000 base pairs
The most N-terminal part of BKV agnoprotein is involved in the interaction with a-SNAP
Presence of BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter
Summary
Polyomaviridae are non-enveloped viruses containing a circular double stranded DNA genome of approximately 5,000 base pairs. A few years ago, two novel polyomaviruses, designated KI virus and WU virus, were found in human nasopharyngeal aspirates [6,7], while a third, not previously described polyomavirus in Merkel cell carcinoma was isolated and named Merkel cell polyomavirus [8]. Last year, another three new human polyomaviruses were reported. The third virus was identified in spicules of trichodysplasia spinulosa (TS) and was named trichodysplasia spinulosa-associated polyomavirus (TSV) [10] This year another human polyomavirus was detected in a kidney transplant patient, and named HPyV9 [11]. The exact function(s) of agnoprotein of BK virus remains elusive
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