Identification of BK Polyomavirus Agnoprotein as a Novel Viroporin

BK polyomavirus (BKPyV) is a small dsDNA virus and a common opportunistic
infection in kidney transplant patients where it causes polyomavirus associated
nephropathy (PVAN). In addition to the standard complement of structural and
non- structural proteins, BKPyV also encodes a small auxiliary protein termed the
agnoprotein. This is a small, highly basic protein that is expressed late during the
viral life cycle. Previous studies have shown that agnoprotein is a novel viral
egress factor. Polyomaviruses lacking agnoprotein show a profound defect in
virus release into cell culture media. Despite these observations the mechanism
by which the agnoprotein regulates such a critical stage in the viral lifecycle is
poorly understood.

In 2010, the agnoprotein encoded for by JC polyomavirus (JCPyV) was shown to
have a viroporin function. Viroporins are a family of virally encoded channel
forming proteins, which are well characterised to have essential functions during
virus egress. Viroporins have become ubiquitous across many viral families and
popular drug targets in many cases. We have developed a detergent-free
purification system for the production of recombinant BKPyV agnoprotein. Using
this system, we have been able to show that this viroporin function is conserved
in BKPyV and that the channel formed is sensitive to classical viroporin inhibitors.