虽然大多数 NOD 样受体 (NLR) 主要由先天免疫细胞表达，但 NLRC3（一种免疫信号传导抑制性 NLR）在淋巴细胞中表现出最高表达。 NLRC3 或任何 NLR 在 B 淋巴细胞中的作用尚不清楚。伽马疱疹病毒，包括人 Epstein-Barr 病毒 (EBV) 和鼠伽马疱疹病毒 68 (MHV-68)，在 B 淋巴细胞中建立潜伏感染，这需要升高的 NF-κB。这项研究表明，在人类 B 细胞的潜伏 EBV 感染过程中，病毒编码的潜伏膜蛋白 1 (LMP1) 会减少 NLRC3 转录。 LMP1 诱导的 NF-κB 激活通过 p65 与启动子结合来抑制 NLRC3 的启动子活性。相反，NLRC3 通过以蛋白酶体依赖性方式促进 LMP1 降解来抑制 NF-κB 激活。在体内，MHV-68感染会减少脾细胞中的Nlrc3转录本，并且Nlrc3缺陷小鼠比对照组表现出更长的病毒潜伏期。这些结果揭示了 B 淋巴细胞中的双向调节回路，其中病毒潜伏蛋白 LMP1 降低 NLRC3 表达，而 NLRC3 破坏伽马疱疹病毒潜伏期，这是肿瘤发生的重要步骤。© 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.© 2024 Wiley Periodicals LLC.