College of Life Sciences, Northwest University, Xi'an, China.
Department of Infectious Diseases, Tangdu Hospital, Air Force Medical University, Xi'an, China.
Viral Immunol. 2024 Jan-Feb;37(1):44-56. doi: 10.1089/vim.2023.0111. Epub 2024 Feb 6.
Hantaan virus (HTNV) is prevalent in Eurasia. It causes hemorrhagic fever with renal syndrome (HFRS). Long noncoding RNAs (lncRNAs) play key roles in regulating innate immunity. Among these, lncRNA negative regulator of interferon response (NRIR) was reported as an inhibitor of several interferon (IFN)-stimulated genes. Our results showed that: NRIR expression was upregulated by HTNV infection in a type I IFN-dependent manner. The expression of NRIR in CD14 monocytes from HFRS patients in acute phase was significantly higher than that in convalescent phase and healthy controls. HTNV infection in some HTNV-compatible cells was promoted by NRIR. NRIR negatively regulated innate immunity, especially IFITM3 expression. Localized in the nucleus, NRIR bound with HNRNPC, and knockdown of HNRNPC significantly weakened the effect of NRIR in promoting HTNV infection and restored IFITM3 expression. These results indicated that NRIR regulates the innate immune response against HTNV infection possibly through its interaction with HNRNPC and its influence on IFITM3.
汉坦病毒（HTNV）在欧亚大陆流行。它引起肾综合征出血热（HFRS）。长链非编码 RNA（lncRNA）在调节先天免疫中起关键作用。其中，lncRNA 干扰素反应的负调控因子（NRIR）被报道为几种干扰素（IFN）-刺激基因的抑制剂。我们的结果表明：NRIR 的表达被 HTNV 感染以依赖 I 型 IFN 的方式上调。HFRS 患者急性期 CD14 单核细胞中 NRIR 的表达明显高于恢复期和健康对照组。NRIR 促进了一些 HTNV 兼容细胞中的 HTNV 感染。NRIR 负调控先天免疫，特别是 IFITM3 的表达。NRIR 定位于核内，与 HNRNPC 结合，敲低 HNRNPC 可显著减弱 NRIR 促进 HTNV 感染的作用，并恢复 IFITM3 的表达。这些结果表明，NRIR 可能通过与 HNRNPC 的相互作用及其对 IFITM3 的影响来调节针对 HTNV 感染的先天免疫反应。
