Temporal proteomic analysis of BK polyomavirus infection reveals virus-induced G2 arrest and highly effective evasion of innate immune sensing.
Authors of this article are:
Caller LG, Davies CTR, Antrobus R, Lehner PJ, Weekes MP, Crump CM.
A summary of the article is shown below:
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 kilobase pair dsDNA genome expresses just seven known proteins, thus it relies heavily on 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 cell throughout 72 hours 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 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.ImportanceBK 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 defence systems. In addition, our data provide an important resource for the future study of kidney epithelial cells and their infection by urinary tract pathogens.Copyright © 2019 Caller et al.
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