Abstract
BK polyomavirus (BKPyV) is a member of a family of potentially oncogenic viruses, whose reactivation can cause severe pathological conditions in transplant patients, leading to graft rejection. As with many non-enveloped viruses, it is assumed that virus release occurs through lysis of the host cell. We now show the first evidence for a non-lytic release pathway for BKPyV and that this pathway can be blocked by the anion channel inhibitor DIDS. Our data show a dose-dependent effect of DIDS on the release of BKPyV virions. We also observed an accumulation of viral capsids in large LAMP-1-positive acidic organelles within the cytoplasm of cells upon DIDS treatment, suggesting potential late endosome or lysosome-related compartments are involved in non-lytic BKPyV release. These data highlight a novel mechanism by which polyomaviruses can be released from infected cells in an active and non-lytic manner, and that anion homeostasis regulation is important in this pathway.
Highlights
BK polyomavirus (BKPyV) was identified in 1971 at a similar time to JC polyomavirus (JCPyV) [1,2], and these were the only human polyomaviruses to be isolated until 2007
The effect of DIDS on BKPyV release was tested in renal proximal tubule epithelial (RPTE) cells, a primary human cell line that supports efficient replication of BKPyV and the closest cell culture system to the natural site of infection for BKPyV currently available [41]
Polyomaviruses are becoming of increasing interest as our reliance on immunosuppressive therapies rises, and the discovery of new human polyomaviruses creates the possibility of these viruses being a significant risk factor for pathological conditions
Summary
BK polyomavirus (BKPyV) was identified in 1971 at a similar time to JC polyomavirus (JCPyV) [1,2], and these were the only human polyomaviruses to be isolated until 2007. Since 11 other human polyomaviruses have been discovered, including Merkel cell polyomavirus, thought to be the major cause of Merkel cell carcinoma, rare but aggressive tumours [3,4]. Their oncogenic potential alongside the discovery of many new polyomaviruses has led to renewed interest in these viruses, and has resulted in a revision of the polyomavirus taxonomy. BKPyV can re-activate in kidney transplant patients after immunosuppression, leading to polyomavirus-associated nephropathy (PVAN). The drugs most frequently used to target BKPyV in PVAN and HC are cidofovir and leflunomide, which, while being effective for HC [15], are nephrotoxic and
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