Epstein-Barr virus lytic gene BNRF1 promotes B-cell lymphomagenesis via IFI27 upregulation
Copyright: © 2024 Sagou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..
Epstein-Barr virus (EBV) is a ubiquitous human lymphotropic herpesvirus that is causally associated with several malignancies. In addition to latent factors, lytic replication contributes to cancer development. In this study, we examined whether the lytic gene BNRF1, which is conserved among gamma-herpesviruses, has an important role in lymphomagenesis. We found that lymphoblastoid cell lines (LCLs) established by BNRF1-knockout EBV exhibited remarkably lower pathogenicity in a mice xenograft model than LCLs produced by wild-type EBV (LCLs-WT). RNA-seq analyses revealed that BNRF1 elicited the expression of interferon-inducible protein 27 (IFI27), which promotes cell proliferation. IFI27 knockdown in LCLs-WT resulted in excessive production of reactive oxygen species, leading to cell death and significantly decreased their pathogenicity in vivo. We also confirmed that IFI27 was upregulated during primary infection in B-cells. Our findings revealed that BNRF1 promoted robust proliferation of the B-cells that were transformed by EBV latent infection via IFI27 upregulation both in vitro and in vivo.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
PLoS pathogens - 20(2024), 2 vom: 06. Feb., Seite e1011954 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sagou, Ken [VerfasserIn] |
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| Links: |
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| Themen: |
9008-11-1 |
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| Anmerkungen: |
Date Completed 05.02.2024 Date Revised 05.02.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.ppat.1011954 |
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| funding: |
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| PPN (Katalog-ID): |
NLM367902818 |
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| 520 | |a Copyright: © 2024 Sagou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||
| 520 | |a Epstein-Barr virus (EBV) is a ubiquitous human lymphotropic herpesvirus that is causally associated with several malignancies. In addition to latent factors, lytic replication contributes to cancer development. In this study, we examined whether the lytic gene BNRF1, which is conserved among gamma-herpesviruses, has an important role in lymphomagenesis. We found that lymphoblastoid cell lines (LCLs) established by BNRF1-knockout EBV exhibited remarkably lower pathogenicity in a mice xenograft model than LCLs produced by wild-type EBV (LCLs-WT). RNA-seq analyses revealed that BNRF1 elicited the expression of interferon-inducible protein 27 (IFI27), which promotes cell proliferation. IFI27 knockdown in LCLs-WT resulted in excessive production of reactive oxygen species, leading to cell death and significantly decreased their pathogenicity in vivo. We also confirmed that IFI27 was upregulated during primary infection in B-cells. Our findings revealed that BNRF1 promoted robust proliferation of the B-cells that were transformed by EBV latent infection via IFI27 upregulation both in vitro and in vivo | ||
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| 650 | 7 | |a IFI27 protein, human |2 NLM | |
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| 700 | 1 | |a Sato, Yoshitaka |e verfasserin |4 aut | |
| 700 | 1 | |a Okuno, Yusuke |e verfasserin |4 aut | |
| 700 | 1 | |a Watanabe, Takahiro |e verfasserin |4 aut | |
| 700 | 1 | |a Inagaki, Tomoki |e verfasserin |4 aut | |
| 700 | 1 | |a Motooka, Yashiro |e verfasserin |4 aut | |
| 700 | 1 | |a Toyokuni, Shinya |e verfasserin |4 aut | |
| 700 | 1 | |a Murata, Takayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Kiyoi, Hitoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Kimura, Hiroshi |e verfasserin |4 aut | |
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