Elimination of LMP1-expressing cells from a monolayer of gastric cancer AGS cells

Sato, Yoshitaka; Ochiai, Satoru; Murata, Takayuki; Kanda, Teru; Goshima, Fumi; Kimura, Hiroshi

doi:10.18632/oncotarget.16996

Cited by 17 publications

(15 citation statements)

References 36 publications

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“…Accumulating evidence shows the abortive lytic cycle as a third state of EBV infection occurring in the pre-latent phase of EBV primary infection ( Wen et al, 2007 ; Kalla et al, 2010 ; Jochum et al, 2012a , b ; Sato et al, 2017 ; Wang et al, 2019 ) and within EBV-associated tumors ( Hong et al, 2005 , 2009 ; Murata et al, 2019 ; Okuno et al, 2019 ). In this state, the full lytic program is not induced due to an incomplete expression cascade of viral lytic genes; thus, infectious particles are not produced.…”

Section: Introductionmentioning

confidence: 99%

Direct Evidence of Abortive Lytic Infection-Mediated Establishment of Epstein-Barr Virus Latency During B-Cell Infection

et al. 2021

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Viral infection induces dynamic changes in transcriptional profiles. Virus-induced and antiviral responses are intertwined during the infection. Epstein-Barr virus (EBV) is a human gammaherpesvirus that provides a model of herpesvirus latency. To measure the transcriptome changes during the establishment of EBV latency, we infected EBV-negative Akata cells with EBV-EGFP and performed transcriptome sequencing (RNA-seq) at 0, 2, 4, 7, 10, and 14 days after infection. We found transient downregulation of mitotic division-related genes, reflecting reprogramming of cell growth by EBV, and a burst of viral lytic gene expression in the early phase of infection. Experimental and mathematical investigations demonstrate that infectious virions were not produced in the pre-latent phase, suggesting the presence of an abortive lytic infection. Fate mapping using recombinant EBV provided direct evidence that the abortive lytic infection in the pre-latent phase converges to latent infection during EBV infection of B-cells, shedding light on novel roles of viral lytic gene(s) in establishing latency. Furthermore, we find that the BZLF1 protein, which is a key regulator of reactivation, was dispensable for abortive lytic infection in the pre-latent phase, suggesting the divergent regulation of viral gene expressions from a productive lytic infection.

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Section: Introductionmentioning

confidence: 99%

Direct Evidence of Abortive Lytic Infection-Mediated Establishment of Epstein-Barr Virus Latency During B-Cell Infection

et al. 2021

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“…Although LMP1 plays a crucial role in EBV-mediated malignancies, LMP1 has seldom been detected in EBV-positive gastric tumors. A study by Sato et al ( 2017 ) provides a hint toward the mechanism explaining this controversial observation. They demonstrated that co-culture of LMP1-positive and -negative gastric cancer cells leads to elimination of LMP1-positive cells, through the release of LMP1-loaded exosomes that mediate epidermal growth factor receptor (EGFR) activation in LMP1-negative cells.…”

Section: Exosomesmentioning

confidence: 99%

Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers

et al. 2018

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Emerging evidence suggests that chronic inflammation caused by pathogen infection is connected to the development of various types of cancer. It is estimated that up to 20% of all cancer deaths is linked to infections and inflammation. In gastric cancer, such triggers can be infection of the gastric epithelium by either Helicobacter pylori (H. pylori), a bacterium present in half of the world population; or by Epstein-Barr virus (EBV), a double-stranded DNA virus which has recently been associated with gastric cancer. Both agents can establish lifelong inflammation by evolving to escape immune surveillance and, under certain conditions, contribute to the development of gastric cancer. Non-coding RNAs, mainly microRNAs (miRNAs), influence the host innate and adaptive immune responses, though long non-coding RNAs and viral miRNAs also alter these processes. Reports suggest that chronic infection results in altered expression of host miRNAs. In turn, dysregulated miRNAs modulate the host inflammatory immune response, favoring bacterial survival and persistence within the gastric mucosa. Given the established roles of miRNAs in tumorigenesis and innate immunity, they may serve as an important link between H. pylori- and EBV-associated inflammation and carcinogenesis. Example of this is up-regulation of miR-155 in H. pylori and EBV infection. The tumor environment contains a variety of cells that need to communicate with each other. Extracellular vesicles, especially exosomes, allow these cells to deliver certain type of information to other cells promoting cancer growth and metastasis. Exosomes have been shown to deliver not only various types of genetic information, mainly miRNAs, but also cytotoxin-associated gene A (CagA), a major H. pylori virulence factor. In addition, a growing body of evidence demonstrates that exosomes contain genetic material of viruses and viral miRNAs and proteins such as EBV latent membrane protein 1 (LMP1) which are delivered into recipient cells. In this review, we focus on the dysregulated H. pylori- and EBV-associated miRNAs while trying to unveil possible causal mechanisms. Moreover, we discuss the role of exosomes as vehicles for miRNA delivery in H. pylori- and EBV-related carcinogenesis.

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“…Growth curves were measured as described previously [14]. Briefly, Akata(-) cells were seeded at a density of 1 × 10 5 cells/mL.…”

Section: Methodsmentioning

confidence: 99%

“…The amount of virus particles in the culture supernatant and the number of infected cells were routinely measured as follows: a portion (400 μL) of the infected cell culture was routinely harvested, and the amount of released infectious virions in the culture supernatant was quantified as described previously [46]. The cell number was counted as described previously [14]. The percentage of infected cells was quantified by FACS [46].…”

Section: Methodsmentioning

confidence: 99%

Direct evidence of abortive lytic infection-mediated establishment of Epstein-Barr virus latency during B-cell infection

Inagaki

Sato

Ito

et al. 2020

Preprint

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36 Viral infection induces dynamic changes in transcriptional profiles. Virus-37 induced and anti-viral responses are intertwined during the infection. Epstein-38 Barr virus (EBV) is a human gammaherpesvirus that provides a model of 39 herpesvirus latency. To measure the transcriptome changes during the 40 establishment of EBV latency, EBV-negative Akata cells were infected with 41 EBV-EGFP and observed by transcriptome sequencing (RNA-seq) at 0, 2, 4, 7, 42 10, and 14 days after infection. We found transient downregulation of mitotic 43 division-related genes, reflecting reprograming of cell growth by EBV. Moreover, 44 a burst of viral lytic gene expression was detected in the early phase of 45 infection. Experimental and mathematical investigations demonstrated that 46 infectious virions were not produced in the pre-latent phase, suggesting the 47 presence of an abortive lytic infection. Finally, we conducted fate mapping using 48 recombinant EBV, enabling the noninvasive, continuous observation of infected 49 cells during EBV infection. Our tracking analysis provided direct evidence that 50 the abortive lytic infection in the pre-latent phase converges to latent infection 51 during EBV infection of B-cells, shedding light on novel roles of viral lytic 52 gene(s) in establishing latency. 53 54 Author summary 55Viral infection is a complex process that activates both virus-triggered and 56 host anti-viral responses. This process has classically been studied by snapshot 57 analysis such as microarray and RNA-seq at discrete time points as population 58 averages. Snapshot data lead to invaluable findings in host-pathogen 59 interactions. However, these "snapshot" omics, even from a single cell, lack 60 temporal resolution. Because the behavior of infected cells is highly dynamic 61 and heterogenous, continuous analysis is required for deciphering the fate of 62 infected cells during viral infection. Here, we exploited fate mapping techniques 63 with recombinant Epstein-Barr virus (EBV) to track the infected cells and 64 recorded a log of lytic gene expression during EBV infection. Our continuous 65 observation of infected cells revealed that EBV established latency in B-cells via 66 an abortive lytic infection in the pre-latent phase. 67 PubMed PMID: 19553389. 595

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Elimination of LMP1-expressing cells from a monolayer of gastric cancer AGS cells

Cited by 17 publications

References 36 publications

Direct Evidence of Abortive Lytic Infection-Mediated Establishment of Epstein-Barr Virus Latency During B-Cell Infection

Direct Evidence of Abortive Lytic Infection-Mediated Establishment of Epstein-Barr Virus Latency During B-Cell Infection

Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers

Direct evidence of abortive lytic infection-mediated establishment of Epstein-Barr virus latency during B-cell infection

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