송문정 (고려대학교)

한빛사논문

조회424

고려대학교

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J. Med. Virol., Mar 2024, 96 (3) | https://doi.org/10.1002/jmv.29504 Dynamic bidirectional regulation of NLRC3 and gammaherpesviruses during viral latency in B lymphocytes

Hye-Ri Kang ¹, Ji Ho Han¹, Yee Ching Ng ¹, Seungbo Ryu ¹, Ji-Yeon Park ¹, Woo-Chang Chung ¹, Yoon-Jae Song², Szu-Ting Chen ^3,4,5, W June Brickey ⁴, Jenny P-Y Ting ⁴, Moon Jung Song ¹

¹Virus-Host Interactions Laboratory, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.

²Department of Life Science, Gachon University, Seongnam-Si, Kyeonggi-Do, Republic of Korea.

³Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

⁴Department of Genetics, Lineberger Comprehensive Cancer Center, Center for Translational Immunology and the Institute of Inflammatory Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

⁵Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan.

Hye-Ri Kang and Ji Ho Han contributed equally to this study.

CORRESPONDING AUTHOR : Moon Jung Song

Abstract

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.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-03-08)
연구진국내(교신)+국외 연구진
분야 생명과학 > 감염생물학

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