Efficient and reliable establishment of lymphoblastoid cell lines by Epstein-Barr virus transformation from a limited amount of peripheral blood

Omi, Natsue; Tokuda, Yoshiyuki; Ikeda, Yoko; Ueno, Masaki; Mori, Kazuhiko; Sotozono, Chie; Kinoshita, Shigeru; Nakano, Masakazu; Tashiro, Kei

doi:10.1038/srep43833

Cited by 15 publications

(16 citation statements)

References 21 publications

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“…Studies have shown that chronic activation of STAT3 is thought to be triggered by IL-6, which is induced by persistent activation of NF-κB [ 87 , 88 ]. Activation of NF-κB and STAT3 following B lymphocyte infection with EBV in vitro leads to the induction of chronic inflammation, which is critical for the continuous proliferation of infected B cells and the establishment of lymphoblastoid cell lines (LCLs) [ 89 , 90 ]. During this latency, known as latency type III, a total of nine genes are expressed, including EBV-encoded RNAs (EBER 1 and 2), EBV nuclear antigens (EBNAs 1, 2, 3A, 3B, 3C, and LP) and EBV latent membrane proteins (LMPs 1, 2A, and 2B).…”

Section: Role Of Csms In the Induction Of Inflammation During Ebvmentioning

confidence: 99%

Lymphotropic Viruses: Chronic Inflammation and Induction of Cancers

Harhaj

Shembade

2020

Biology

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Inflammation induced by transcription factors, including Signal Transducers and Activators of Transcription (STATs) and NF-κB, in response to microbial pathogenic infections and ligand dependent receptors stimulation are critical for controlling infections. However, uncontrolled inflammation induced by these transcription factors could lead to immune dysfunction, persistent infection, inflammatory related diseases and the development of cancers. Although the induction of innate immunity and inflammation in response to viral infection is important to control virus replication, its effects can be modulated by lymphotropic viruses including human T-cell leukemia virus type 1 (HTLV-1), Κaposi’s sarcoma herpesvirus (KSHV), and Epstein Barr virus (EBV) during de novo infection as well as latent infection. These lymphotropic viruses persistently activate JAK-STAT and NF-κB pathways. Long-term STAT and NF-κB activation by these viruses leads to the induction of chronic inflammation, which can support the persistence of these viruses and promote virus-mediated cancers. Here, we review how HTLV-1, KSHV and EBV hijack the function of host cell surface molecules (CSMs), which are involved in the regulation of chronic inflammation, innate and adaptive immune responses, cell death and the restoration of tissue homeostasis. Thus, better understanding of CSMs-mediated chronic activation of STATs and NF-κB pathways in lymphotropic virus-infected cells may pave the way for therapeutic intervention in malignancies caused by lymphotropic viruses.

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Section: Role Of Csms In the Induction Of Inflammation During Ebvmentioning

confidence: 99%

Lymphotropic Viruses: Chronic Inflammation and Induction of Cancers

Harhaj

Shembade

2020

Biology

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“…A large part of our current understanding of the biology of EBV is based on in vitro studies of infection of human B-lymphocytes. In vitro infection of B-cells leads to their immortalization 1 . In these cells, the virus establishes a latent infection, in which upto 11 viral products, namely 6 Epstein-Barr nuclear antigens (EBNA1, EBNA2, EBNA3a, EBNA3b, EBNA3c, EBNA-LP), 3 latent membrane proteins (LMP1, LMP2a, LMP2b) and large quantities of two non-protein encoding RNAs (EBER-1 and EBER-2) are expressed 2 .…”

Section: Introductionmentioning

confidence: 99%

Uncovering early events in primary Epstein-Barr virus infection using a rabbit model

Reguraman

Hassani

Philip

et al. 2021

Sci Rep

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Epstein-Barr virus (EBV) is an oncogenic herpesvirus implicated in the pathogenesis of several malignant and non-malignant conditions. However, a number of fundamental aspects about the biology of EBV and the mechanism(s) by which this virus induces pathology remain unknown. One major obstacle has been the lack of a suitable animal model for EBV infection. In this study, using our recently established rabbit model of EBV infection, we examined the early events following primary EBV infection. We show that, both immunocompetent and immunosuppressed animals were readily susceptible to EBV infection. However, immunosuppressed animals showed marked splenomegaly and widespread infection. Following EBV infection, the virus primarily targeted naïve IgM+, CD20+, CD21+ and CD79a+ B cells. Infected cells expressed varying sets of viral latent/lytic gene products. Notably, co-expression of latent and lytic proteins in the same cell was not observed. Infected cells in type 0/1 latency (EBERs+), were small and proliferating (Ki67+). By contrast, cells in type 2/3 latency (LMP1+), were large, non-proliferating (Ki-67−) and p53+. Although infected B-cells were widely present in splenic follicles, they did not express germinal center marker, BCL-6. Taken together, this study shows for the first time, some of the early events following primary EBV infection.

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“…EBV infects B-cells and could immortalize the B-cells and form long-term growing LCLs which consistently express the viruses [4]. This method has been used in laboratories to immortalize certain human blood-derived B-cells which can be later on used as a culture model for various studies including large-scale drug library screening, vaccine study, and high throughput biological studies [5, 6].…”

Section: Introductionmentioning

confidence: 99%

“…In the past decades, researchers have put in effort to improve the immortalization method and its efficiency [7]. Recently, it has been shown that with a minor modification, LCLs could be generated from a small volume of peripheral blood as low as 0.1mL [4]. This finding is particularly useful under a circumstance in which the sample volume is limited.…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus- (EBV-) Immortalized Lymphoblastoid Cell Lines (LCLs) Express High Level of CD23 but Low CD27 to Support Their Growth

Yap

Siow

Chow

et al. 2019

Advances in Virology

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Epstein-Barr virus (EBV) is one of the common human herpesvirus types in the world. EBV is known to infect more than 95% of adults in the world. The virus mainly infects B lymphocytes and could immortalize and transform the cells into EBV-bearing lymphoblastoid cell lines (LCLs). Limited studies have been focused on characterizing the surface marker expression of the immortalized LCLs. This study demonstrates the generation of 15 LCLs from sixteen rheumatoid arthritis (RA) patients and a healthy volunteer using B95-8 marmoset-derived EBV. The success rate of LCL generation was 88.23%. All CD19+ LCLs expressed CD23 (16.94-58.9%) and CD27 (15.74-80.89%) on cell surface. Our data demonstrated two distinct categories of LCLs (fast- and slow-growing) (p<0.05) based on their doubling time. The slow-growing LCLs showed lower CD23 level (35.28%) compared to fast-growing LCLs (42.39%). In contrast, the slow-growing LCLs showed higher percentage in both CD27 alone and CD23+CD27+ in combination. Overall, these findings may suggest the correlations of cellular CD23 and CD27 expression with the proliferation rate of the generated LCLs. Increase expression of CD23 may play a role in EBV immortalization of B-cells and the growth and maintenance of the EBV-transformed LCLs while CD27 expression might have inhibitory effects on LCL proliferation. Further investigations are warranted to these speculations.

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Efficient and reliable establishment of lymphoblastoid cell lines by Epstein-Barr virus transformation from a limited amount of peripheral blood

Cited by 15 publications

References 21 publications

Lymphotropic Viruses: Chronic Inflammation and Induction of Cancers

Lymphotropic Viruses: Chronic Inflammation and Induction of Cancers

Uncovering early events in primary Epstein-Barr virus infection using a rabbit model

Epstein-Barr Virus- (EBV-) Immortalized Lymphoblastoid Cell Lines (LCLs) Express High Level of CD23 but Low CD27 to Support Their Growth

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