The First Affiliated Hospital, Biomedical Translational Research Institute, The International Immunology Center and The Key Laboratory of Antibody Engineering of Guangdong Province, Jinan University, Guangzhou, Guangdong Province, China.
Department of Developmental and Regenerative Biology, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong Province, China.
J Immunol Res. 2018 Jul 5;2018:5214187. doi: 10.1155/2018/5214187. eCollection 2018.
The innate immune response is the first line defense against viral infections. Novel genes involved in this system are continuing to emerge. SLC15A3, a proton-coupled histidine and di-tripeptide transporter that was previously found in lysosomes, has been reported to inhibit chikungunya viral replication in host cells. In this study, we found that SLC15A3 was significantly induced by DNA virus herpes simplex virus-1(HSV-1) in monocytes from human peripheral blood mononuclear cells. Aside from monocytes, it can also be induced by HSV-1 in 293T, HeLa cells, and HaCaT cells. Overexpression of SLC15A3 in 293T cells inhibits HSV-1 replication and enhances type I and type III interferon (IFN) responses, while silencing SLC15A3 leads to enhanced HSV-1 replication with reduced IFN production. Moreover, we found that SLC15A3 interacted with MAVS and STING and potentiated MAVS- and STING-mediated IFN production. These results demonstrate that SLC15A3 participates in anti-HSV-1 innate immune responses by regulating MAVS- and STING-mediated signaling pathways.
先天免疫反应是抵御病毒感染的第一道防线。新的参与该系统的基因不断涌现。SLC15A3 是一种质子偶联的组氨酸和二肽转运蛋白，以前在溶酶体中发现，据报道可抑制宿主细胞中的基孔肯雅病毒复制。在这项研究中，我们发现 DNA 病毒单纯疱疹病毒 1（HSV-1）可在人外周血单核细胞中的单核细胞中显著诱导 SLC15A3。除单核细胞外，HSV-1 还可以诱导 293T、HeLa 和 HaCaT 细胞中 SLC15A3 的诱导。在 293T 细胞中过表达 SLC15A3 可抑制 HSV-1 复制并增强 I 型和 III 型干扰素（IFN）反应，而沉默 SLC15A3 则导致 IFN 产生减少的 HSV-1 复制增强。此外，我们发现 SLC15A3 与 MAVS 和 STING 相互作用，并增强 MAVS 和 STING 介导的 IFN 产生。这些结果表明，SLC15A3 通过调节 MAVS 和 STING 介导的信号通路参与抗 HSV-1 先天免疫反应。
