scholarly journals Temporal proteomic analysis of BK polyomavirus infection reveals virus-induced G2 arrest and highly effective evasion of innate immune sensing

2019 ◽  
Author(s):  
Laura G. Caller ◽  
Colin T.R. Davies ◽  
Robin Antrobus ◽  
Paul J. Lehner ◽  
Michael P. Weekes ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Innate Immune ◽  
Global Changes ◽  
Renal Transplant Recipients ◽  
G2 Arrest ◽  
Bk Polyomavirus ◽  
Immune Sensing ◽  
Proteome Changes ◽  
Virus Replication Cycle ◽  
Innate Immune Sensing

AbstractBK polyomavirus (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 both 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.

scholarly journals BK Polyomavirus Evades Innate Immune Sensing by Disrupting the Mitochondrial Network and Promotes Mitophagy

iScience ◽  
2020 ◽  
Vol 23 (7) ◽  
pp. 101257 ◽  
Author(s):  
Julia Manzetti ◽  
Fabian H. Weissbach ◽  
Fabrice E. Graf ◽  
Gunhild Unterstab ◽  
Marion Wernli ◽  
...  
Keyword(s):  
Innate Immune ◽  
Mitochondrial Network ◽  
Bk Polyomavirus ◽  
Immune Sensing ◽  
Innate Immune Sensing

scholarly journals Temporal Proteomic Analysis of BK Polyomavirus Infection Reveals Virus-Induced G2Arrest and Highly Effective Evasion of Innate Immune Sensing

2019 ◽  
Vol 93 (16) ◽  
Author(s):  
Laura G. Caller ◽  
Colin T. R. Davies ◽  
Robin Antrobus ◽  
Paul J. Lehner ◽  
Michael P. Weekes ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Urinary Tract ◽  
Epithelial Cells ◽  
Innate Immune ◽  
Replication Cycle ◽  
Global Changes ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Cell Defense ◽  
Bk Polyomavirus

ABSTRACTBK 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-G2arrest 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.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 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.

scholarly journals Special Issue: “Innate Immune Sensing of Viruses and Viral Evasion”

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 567
Author(s):  
Renate König ◽  
Carsten Münk
Keyword(s):  
Innate Immunity ◽  
Innate Immune ◽  
Special Issue ◽  
First Line ◽  
Review Articles ◽  
Immune Sensing ◽  
Innate Immune Sensing ◽  
Viral Evasion

In this Special Issue, a wide variety of original and review articles provide a timely overview of how viruses are recognized by and evade from cellular innate immunity, which represents the first line of defense against viruses [...]

scholarly journals The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype

2018 ◽  
Author(s):  
Priya Hari ◽  
Fraser R. Millar ◽  
Nuria Tarrats ◽  
Jodie Birch ◽  
Curtis J. Rink ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Cycle Arrest ◽  
Secretory Phenotype ◽  
Immune Sensing ◽  
Molecular Patterns ◽  
Innate Immune Sensing

ABSTRACTCellular senescence is a stress response program characterised by a robust cell cycle arrest and the induction of a pro-inflammatory senescence-associated secretory phenotype (SASP) that is triggered through an unknown mechanism. Here, we show that during oncogene-induced senescence (OIS), the Toll-like receptor TLR2 and its partner TLR10 are key mediators of senescence in vitro and in murine models. TLR2 promotes cell cycle arrest by regulating the tumour suppressors p53-p21CIP1, p16INK4a and p15INK4b, and regulates the SASP through the induction of the acute-phase serum amyloids A1 and A2 (A-SAA) that, in turn, function as the damage associated molecular patterns (DAMPs) signalling through TLR2 in OIS. Finally, we found evidence that the cGAS-STING cytosolic DNA sensing pathway primes TLR2 and A-SAA expression in OIS. In summary, we report that innate immune sensing of senescence-associated DAMPs by TLR2 controls the SASP and reinforces the cell cycle arrest program in OIS.

scholarly journals Bloom syndrome protein restrains innate immune sensing of micronuclei by cGAS

2019 ◽  
Vol 216 (5) ◽  
pp. 1199-1213 ◽  
Author(s):  
Matthieu Gratia ◽  
Mathieu P. Rodero ◽  
Cécile Conrad ◽  
Elias Bou Samra ◽  
Mathieu Maurin ◽  
...  
Keyword(s):  
Dna Damage ◽  
Immune Responses ◽  
Genome Instability ◽  
Bloom Syndrome ◽  
Innate Immune ◽  
Genome Integrity ◽  
Immune Sensing ◽  
Syndrome Protein ◽  
Innate Immune Sensing ◽  
Exonuclease Trex1

Cellular innate immune sensors of DNA are essential for host defense against invading pathogens. However, the presence of self-DNA inside cells poses a risk of triggering unchecked immune responses. The mechanisms limiting induction of inflammation by self-DNA are poorly understood. BLM RecQ–like helicase is essential for genome integrity and is deficient in Bloom syndrome (BS), a rare genetic disease characterized by genome instability, accumulation of micronuclei, susceptibility to cancer, and immunodeficiency. Here, we show that BLM-deficient fibroblasts show constitutive up-regulation of inflammatory interferon-stimulated gene (ISG) expression, which is mediated by the cGAS–STING–IRF3 cytosolic DNA–sensing pathway. Increased DNA damage or down-regulation of the cytoplasmic exonuclease TREX1 enhances ISG expression in BLM-deficient fibroblasts. cGAS-containing cytoplasmic micronuclei are increased in BS cells. Finally, BS patients demonstrate elevated ISG expression in peripheral blood. These results reveal that BLM limits ISG induction, thus connecting DNA damage to cellular innate immune response, which may contribute to human pathogenesis.

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