Dynamic bidirectional regulation of NLRC3 and gammaherpesviruses during viral latency in B lymphocytes
© 2024 Wiley Periodicals LLC..
While most NOD-like receptors (NLRs) are predominately expressed by innate immune cells, NLRC3, an inhibitory NLR of immune signaling, exhibits the highest expression in lymphocytes. The role of NLRC3 or any NLRs in B lymphocytes is completely unknown. Gammaherpesviruses, including human Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV-68), establish latent infection in B lymphocytes, which requires elevated NF-κB. This study shows that during latent EBV infection of human B cells, viral-encoded latent membrane protein 1 (LMP1) decreases NLRC3 transcript. LMP1-induced-NF-κB activation suppresses the promoter activity of NLRC3 via p65 binding to the promoter. Conversely, NLRC3 inhibits NF-κB activation by promoting the degradation of LMP1 in a proteasome-dependent manner. In vivo, MHV-68 infection reduces Nlrc3 transcripts in splenocytes, and Nlrc3-deficient mice show greater viral latency than controls. These results reveal a bidirectional regulatory circuit in B lymphocytes, where viral latent protein LMP1 reduces NLRC3 expression, while NLRC3 disrupts gammaherpesvirus latency, which is an important step for tumorigenesis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:96 |
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| Enthalten in: |
Journal of medical virology - 96(2024), 3 vom: 01. März, Seite e29504 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kang, Hye-Ri [VerfasserIn] |
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| Links: |
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| Themen: |
B lymphocytes |
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| Anmerkungen: |
Date Completed 07.03.2024 Date Revised 07.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/jmv.29504 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369356306 |
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| 520 | |a While most NOD-like receptors (NLRs) are predominately expressed by innate immune cells, NLRC3, an inhibitory NLR of immune signaling, exhibits the highest expression in lymphocytes. The role of NLRC3 or any NLRs in B lymphocytes is completely unknown. Gammaherpesviruses, including human Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV-68), establish latent infection in B lymphocytes, which requires elevated NF-κB. This study shows that during latent EBV infection of human B cells, viral-encoded latent membrane protein 1 (LMP1) decreases NLRC3 transcript. LMP1-induced-NF-κB activation suppresses the promoter activity of NLRC3 via p65 binding to the promoter. Conversely, NLRC3 inhibits NF-κB activation by promoting the degradation of LMP1 in a proteasome-dependent manner. In vivo, MHV-68 infection reduces Nlrc3 transcripts in splenocytes, and Nlrc3-deficient mice show greater viral latency than controls. These results reveal a bidirectional regulatory circuit in B lymphocytes, where viral latent protein LMP1 reduces NLRC3 expression, while NLRC3 disrupts gammaherpesvirus latency, which is an important step for tumorigenesis | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a EBV | |
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| 650 | 4 | |a NLRC3 | |
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| 700 | 1 | |a Han, Ji Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Ng, Yee Ching |e verfasserin |4 aut | |
| 700 | 1 | |a Ryu, Seungbo |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Ji-Yeon |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Woo-Chang |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Yoon-Jae |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Szu-Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Brickey, W June |e verfasserin |4 aut | |
| 700 | 1 | |a Ting, Jenny P-Y |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Moon Jung |e verfasserin |4 aut | |
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