Cargando…

Temporal Proteomic Analysis of BK Polyomavirus Infection Reveals Virus-Induced G(2) Arrest and Highly Effective Evasion of Innate Immune Sensing

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Caller, Laura G., Davies, Colin T. R., Antrobus, Robin, Lehner, Paul J., Weekes, Michael P., Crump, Colin M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675895/
https://www.ncbi.nlm.nih.gov/pubmed/31142673
http://dx.doi.org/10.1128/JVI.00595-19
_version_ 1783440676312055808
author Caller, Laura G.
Davies, Colin T. R.
Antrobus, Robin
Lehner, Paul J.
Weekes, Michael P.
Crump, Colin M.
author_facet Caller, Laura G.
Davies, Colin T. R.
Antrobus, Robin
Lehner, Paul J.
Weekes, Michael P.
Crump, Colin M.
author_sort Caller, Laura G.
collection PubMed
description 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-G(2) 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.
format Online
Article
Text
id pubmed-6675895
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher American Society for Microbiology
record_format MEDLINE/PubMed
spelling pubmed-66758952019-08-08 Temporal Proteomic Analysis of BK Polyomavirus Infection Reveals Virus-Induced G(2) Arrest and Highly Effective Evasion of Innate Immune Sensing Caller, Laura G. Davies, Colin T. R. Antrobus, Robin Lehner, Paul J. Weekes, Michael P. Crump, Colin M. J Virol Virus-Cell Interactions 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-G(2) 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. American Society for Microbiology 2019-07-30 /pmc/articles/PMC6675895/ /pubmed/31142673 http://dx.doi.org/10.1128/JVI.00595-19 Text en Copyright © 2019 Caller et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Virus-Cell Interactions
Caller, Laura G.
Davies, Colin T. R.
Antrobus, Robin
Lehner, Paul J.
Weekes, Michael P.
Crump, Colin M.
Temporal Proteomic Analysis of BK Polyomavirus Infection Reveals Virus-Induced G(2) Arrest and Highly Effective Evasion of Innate Immune Sensing
title Temporal Proteomic Analysis of BK Polyomavirus Infection Reveals Virus-Induced G(2) Arrest and Highly Effective Evasion of Innate Immune Sensing
title_full Temporal Proteomic Analysis of BK Polyomavirus Infection Reveals Virus-Induced G(2) Arrest and Highly Effective Evasion of Innate Immune Sensing
title_fullStr Temporal Proteomic Analysis of BK Polyomavirus Infection Reveals Virus-Induced G(2) Arrest and Highly Effective Evasion of Innate Immune Sensing
title_full_unstemmed Temporal Proteomic Analysis of BK Polyomavirus Infection Reveals Virus-Induced G(2) Arrest and Highly Effective Evasion of Innate Immune Sensing
title_short Temporal Proteomic Analysis of BK Polyomavirus Infection Reveals Virus-Induced G(2) Arrest and Highly Effective Evasion of Innate Immune Sensing
title_sort temporal proteomic analysis of bk polyomavirus infection reveals virus-induced g(2) arrest and highly effective evasion of innate immune sensing
topic Virus-Cell Interactions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675895/
https://www.ncbi.nlm.nih.gov/pubmed/31142673
http://dx.doi.org/10.1128/JVI.00595-19
work_keys_str_mv AT callerlaurag temporalproteomicanalysisofbkpolyomavirusinfectionrevealsvirusinducedg2arrestandhighlyeffectiveevasionofinnateimmunesensing
AT daviescolintr temporalproteomicanalysisofbkpolyomavirusinfectionrevealsvirusinducedg2arrestandhighlyeffectiveevasionofinnateimmunesensing
AT antrobusrobin temporalproteomicanalysisofbkpolyomavirusinfectionrevealsvirusinducedg2arrestandhighlyeffectiveevasionofinnateimmunesensing
AT lehnerpaulj temporalproteomicanalysisofbkpolyomavirusinfectionrevealsvirusinducedg2arrestandhighlyeffectiveevasionofinnateimmunesensing
AT weekesmichaelp temporalproteomicanalysisofbkpolyomavirusinfectionrevealsvirusinducedg2arrestandhighlyeffectiveevasionofinnateimmunesensing
AT crumpcolinm temporalproteomicanalysisofbkpolyomavirusinfectionrevealsvirusinducedg2arrestandhighlyeffectiveevasionofinnateimmunesensing