Arthritis Center of Nebraska, Lincoln, Nebraska, United States of America.
PLoS One. 2012;7(8):e43317. doi: 10.1371/journal.pone.0043317. Epub 2012 Aug 31.
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus. Toll-like receptor 7 (TLR7) is involved in host innate immunity against pathogens, and its aberrant activation is linked to the development of systemic lupus erythematosus (SLE, also called "lupus"). Type I interferons (IFN) are apparently driving forces for lupus pathogenesis. Previously, we found that EBV latent membrane protein 1 (LMP1) primes cells for IFN production. In this report, the relationship among EBV LMP1, TLRs, and IFN production are examined. We find that TLR7 activation increases the expression of EBV LMP1, and IFN regulatory factor 7 (IRF7) is involved in the stimulation process. TLR7 activation did not induce IFNs from EBV-infected cells, but potentiates those cells for IFN production by TLR3 or TLR9 activation. In addition, we find that LMP1 and IFNs are co-expressed in the same cells in some lupus patients. Therefore, the aberrant activation of TLR7 might induce LMP1 expression and LMP1-expression cells may be producing IFNs in lupus patients. These results suggest EBV might be an exacerbating factor in some lupus patients via promoting IFN production.
EB 病毒（EBV）是一种普遍存在的人类疱疹病毒。Toll 样受体 7（TLR7）参与宿主固有免疫防御病原体，其异常激活与系统性红斑狼疮（SLE，也称为“狼疮”）的发生有关。I 型干扰素（IFN）显然是狼疮发病机制的驱动力。此前，我们发现 EBV 潜伏膜蛋白 1（LMP1）可使细胞产生 IFN。在本报告中，我们研究了 EBV LMP1、TLR 与 IFN 产生之间的关系。我们发现 TLR7 激活可增加 EBV LMP1 的表达，IRF7 参与了刺激过程。TLR7 激活不会诱导 EBV 感染细胞产生 IFNs，但可增强这些细胞对 TLR3 或 TLR9 激活产生 IFN 的能力。此外，我们发现一些狼疮患者中 LMP1 和 IFNs 可在同一细胞中共同表达。因此，TLR7 的异常激活可能会诱导 LMP1 表达，并且 LMP1 表达细胞可能在狼疮患者中产生 IFNs。这些结果表明，EBV 可能通过促进 IFN 产生而成为某些狼疮患者的加重因素。
