Murine Norovirus Replication Induces G<sub>0</sub>/G<sub>1</sub>Cell Cycle Arrest in Asynchronously Growing Cells

Davies, Colin; Brown, Chris M.; Westphal, Dana; Ward, John; Ward, Vernon K.

doi:10.1128/jvi.03673-14

Cited by 32 publications

(45 citation statements)

References 42 publications

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“…MNV infection was performed in triplicate, at an MOI of 5 for 12 h as described previously [28]. Control cells were mock infected with media alone.…”

Section: Methodsmentioning

confidence: 99%

Transcriptomic analysis of human norovirus NS1-2 protein highlights a multifunctional role in murine monocytes

et al. 2017

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BackgroundThe GII.4 Sydney 2012 strain of human norovirus (HuNoV) is a pandemic strain that is responsible for the majority of norovirus outbreaks in healthcare settings. The function of the non-structural (NS)1-2 protein from HuNoV is unknown.Results In silico analysis of human norovirus NS1-2 protein showed that it shares features with the murine NS1-2 protein, including a disordered region, a transmembrane domain and H-box and NC sequence motifs. The proteins also contain caspase cleavage and phosphorylation sites, indicating that processing and phosphorylation may be a conserved feature of norovirus NS1-2 proteins. In this study, RNA transcripts of human and murine norovirus full-length and the disordered region of NS1-2 were transfected into monocytes, and next generation sequencing was used to analyse the transcriptomic profile of cells expressing virus proteins. The profiles were then compared to the transcriptomic profile of MNV-infected cells.ConclusionsRNAseq analysis showed that NS1-2 proteins from human and murine noroviruses affect multiple immune systems (chemokine, cytokine, and Toll-like receptor signaling) and intracellular pathways (NFκB, MAPK, PI3K-Akt signaling) in murine monocytes. Comparison to the transcriptomic profile of MNV-infected cells indicated the pathways that NS1-2 may affect during norovirus infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3417-4) contains supplementary material, which is available to authorized users.

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“…MNV infection was performed in triplicate, at an MOI of 5 for 12 h as described previously [28]. Control cells were mock infected with media alone.…”

Section: Methodsmentioning

confidence: 99%

Transcriptomic analysis of human norovirus NS1-2 protein highlights a multifunctional role in murine monocytes

et al. 2017

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“…Cell cycle analysis by flow cytometry. Nuclear DNA content was measured by propidium iodide staining and fluorescence-activated cell sorting (FACS) as previously described [20]. Briefly, cells were scraped, washed in dPBS and fixed in 3 ml of cold 70% absolute ethanol overnight.…”

Section: Cell Cycle Analysismentioning

confidence: 99%

“…Many viruses can subvert the host cell division in order to create an environment where viral propagation is preferred. Several RNA viruses, including murine norovirus 1 (MNV-1) have been characterized to manipulate cell cycle progression at the G 1 /S restriction point, often creating favorable conditions for viral replication [14][15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Expression of the NS5 (VPg) Protein of Murine Norovirus Induces a G1/S Phase Arrest

Davies

Ward

2016

PLoS ONE

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Murine norovirus-1 (MNV-1) is known to subvert host cell division inducing an accumulation of cells in the G0/G1 phase, creating conditions where viral replication is favored. This study identified that NS5 (VPg), is capable of inducing cell cycle arrest in the absence of viral replication or other viral proteins in an analogous manner to MNV-1 infection. NS5 expression induced an accumulation of cells in the G0/G1 phase in an asynchronous population by inhibiting progression at the G1/S restriction point. Furthermore, NS5 expression resulted in a down-regulation of cyclin A expression in asynchronous cells and inhibited cyclin A expression in cells progressing from G1 to S phase. The activity of NS5 on the host cell cycle occurs through an uncharacterized function. Amino acid substitutions of NS5(Y26A) and NS5(F123A) that inhibit the ability for NS5 to attach to RNA and recruit host eukaryotic translation initiation factors, respectively, retained the ability to induce an accumulation of cells in the G0/G1 phase as identified for wild-type NS5. To the best of our knowledge, this is the first report of a VPg protein manipulating the host cell cycle.

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“…Cell cycle arrest also happens in response to damages such as defects occurred during DNA replication, and the state remains until repair takes place. Viruses may take advantage of cell cycle arrest to modulate the expression of viral or cellular genes critical for the completion of their life cycles given the fluctuating cellular protein levels during cell cycle [93], to reduce the immune response, and to avoid early cell apoptosis (e.g. G0/G1) for the benefit of virus survival [94,95].…”

Section: Cell Cycle Arrestmentioning

confidence: 99%

Orchestrated efforts on host network hijacking: Processes governing virus replication

et al. 2020

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With the high pervasiveness of viral diseases, the battle against viruses has never ceased. Here we discuss five cellular processes, namely "autophagy", "programmed cell death", "immune response", "cell cycle alteration", and "lipid metabolic reprogramming", that considerably guide viral replication after host infection in an orchestrated manner. On viral infection, "autophagy" and "programmed cell death" are two dynamically synchronized cell survival programs; "immune response" is a cell defense program typically suppressed by viruses; "cell cycle alteration" and "lipid metabolic reprogramming" are two altered cell housekeeping programs tunable in both directions. We emphasize on their functionalities in modulating viral replication, strategies viruses have evolved to tune these processes for their benefit, and how these processes orchestrate and govern cell fate upon viral infection. Understanding how viruses hijack host networks has both academic and industrial values in providing insights toward therapeutic strategy design for viral disease control, offering useful information in applications that aim to use viral vectors to improve human health such as gene therapy, and providing guidelines to maximize viral particle yield for improved vaccine production at a reduced cost. ARTICLE HISTORY

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Murine Norovirus Replication Induces G₀/G₁Cell Cycle Arrest in Asynchronously Growing Cells

Cited by 32 publications

References 42 publications

Transcriptomic analysis of human norovirus NS1-2 protein highlights a multifunctional role in murine monocytes

Transcriptomic analysis of human norovirus NS1-2 protein highlights a multifunctional role in murine monocytes

Expression of the NS5 (VPg) Protein of Murine Norovirus Induces a G1/S Phase Arrest

Orchestrated efforts on host network hijacking: Processes governing virus replication

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Murine Norovirus Replication Induces G0/G1Cell Cycle Arrest in Asynchronously Growing Cells

Cited by 32 publications

References 42 publications

Transcriptomic analysis of human norovirus NS1-2 protein highlights a multifunctional role in murine monocytes

Transcriptomic analysis of human norovirus NS1-2 protein highlights a multifunctional role in murine monocytes

Expression of the NS5 (VPg) Protein of Murine Norovirus Induces a G1/S Phase Arrest

Orchestrated efforts on host network hijacking: Processes governing virus replication

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Murine Norovirus Replication Induces G₀/G₁Cell Cycle Arrest in Asynchronously Growing Cells