Abstract
BK polyomavirus (BKPyV; hereafter referred to as BK) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein fail to release from host cells and do not propagate to wild-type levels. Despite this, agnoprotein is not essential for virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-soluble N-ethylmaleimide sensitive fusion (NSF) attachment protein (α-SNAP) is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell.
Highlights
Polyomaviruses are small, non-enveloped viruses that use mammals, fish and birds as their hosts [1,2,3,4]
Agnoprotein is thought to be essential at several stages in the polyomavirus life cycle
Equal amounts of wild type (WT) and ∆Agno genomes were transfected into primary renal proximal tubular epithelial (RPTE) cells, a physiologically relevant cell model for BK infection, and levels of BK protein expression determined at 72 h post transfection
Summary
Polyomaviruses are small, non-enveloped viruses that use mammals, fish and birds as their hosts [1,2,3,4]. Thirteen human polyomaviruses have been discovered and a number are linked to disease [5,6,7]. The first two human polyomaviruses discovered, BK polyomavirus and JC polyomavirus (JCPyV; hereafter referred to as JC), were named after the index case patients upon their discovery more than 40 years ago [8,9] and cause disease in immunosuppressed patients. JC is the causative agent of the lethal brain disease progressive multifocal leukoencephalopathy. BK is an opportunistic pathogen, and is associated with several diseases in the immunosuppressed [10]. Whilst reactivation of BK does occur in healthy individuals, this is usually associated with asymptomatic low-level urinary shedding [12]
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