Abstract
BK polyomavirus (BKPyV) is a small DNA virus that establishes a life-long persistent infection in the urinary tract of most people. BKPyV is known to cause severe morbidity in renal transplant recipients and can lead to graft rejection. The simple 5.2-kbp double-stranded DNA (dsDNA) genome expresses just seven known proteins; thus, it relies heavily on the host machinery to replicate. How the host proteome changes over the course of infection is key to understanding this host-virus interplay. Here, for the first time quantitative temporal viromics has been used to quantify global changes in >9,000 host proteins in two types of primary human epithelial cells throughout 72 h of BKPyV infection. These data demonstrate the importance of cell cycle progression and pseudo-G2 arrest in effective BKPyV replication, along with a surprising lack of an innate immune response throughout the whole virus replication cycle. BKPyV thus evades pathogen recognition to prevent activation of innate immune responses in a sophisticated manner.IMPORTANCE BK polyomavirus can cause serious problems in immune-suppressed patients, in particular, kidney transplant recipients who can develop polyomavirus-associated kidney disease. In this work, we have used advanced proteomics techniques to determine the changes to protein expression caused by infection of two independent primary cell types of the human urinary tract (kidney and bladder) throughout the replication cycle of this virus. Our findings have uncovered new details of a specific form of cell cycle arrest caused by this virus, and, importantly, we have identified that this virus has a remarkable ability to evade detection by host cell defense systems. In addition, our data provide an important resource for the future study of kidney epithelial cells and their infection by urinary tract pathogens.
Highlights
BK polyomavirus (BKPyV) is a small DNA virus that establishes a lifelong persistent infection in the urinary tract of most people
Cells were infected at a multiplicity of infection (MOI) of 5 infectious units per cell, ensuring greater than 90% infection in both renal proximal tubule epithelial (RPTE) and human urothelial (HU) cells
In this experiment a total of 8,985 cellular and 5/7 viral proteins were quantified in both cell types, providing a global view of changes in protein expression during infection in primary human epithelial cells from the kidney and bladder
Summary
BK polyomavirus (BKPyV) is a small DNA virus that establishes a lifelong persistent infection in the urinary tract of most people. For the first time quantitative temporal viromics has been used to quantify global changes in Ͼ9,000 host proteins in two types of primary human epithelial cells throughout 72 h of BKPyV infection. These data demonstrate the importance of cell cycle progression and pseudo-G2 arrest in effective BKPyV replication, along with a surprising lack of an innate immune response throughout the whole virus replication cycle. We have used advanced proteomics techniques to determine the changes to protein expression caused by infection of two independent primary cell types of the human urinary tract (kidney and bladder) throughout the replication cycle of this virus. The role of agnoprotein is less well understood a wide range of activities have been proposed, including acting as a viroporin, enhancing viral DNA replication through interaction with the processivity factor proliferating cell nuclear antigen (PCNA), and enhancing egress of virions from the nucleus [10, 11]
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