Li Shihao, Li Xuechun, Sun Mingzhe, Li Fuhua
State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.
Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, China.
PLoS Pathog. 2025 Aug 18;21(8):e1013433. doi: 10.1371/journal.ppat.1013433. eCollection 2025 Aug.
Intracellular recognition of viral nucleic acids by NLRs and subsequent activation of antiviral immunity are crucial for host defense against virus infection in vertebrates. However, understanding on these processes is very limited in invertebrates, especially for crustaceans. In the present study, an NLR gene belonging to the NLRC subfamily (LvNLRC) was identified in the Pacific whiteleg shrimp Litopenaeus vannamei and its functions in intracellular recognition to DNA virus and antiviral immunity during WSSV infection were elucidated. LvNLRC possesses an ability to detect DNA viral mimics such as poly(dA:dT) with a dose-dependent manner through its leucine-rich repeat (LRR) domain. The LRRs domain also recognizes the partial DNA encoding VP24 of WSSV. LvNLRC could modulate the interferon system-like antiviral response in shrimp through direct interaction between its NACHT domain and LvSTING. Different from the regulatory mechanism in vertebrates, the presence of poly(dA:dT) does not affect the release of STING from the NACHT domain of LvNLRC in shrimp. Interestingly, shrimp Cyclophilin A (LvCypA) can directly interact with the NACHT domain of LvNLRC in a dose-dependent manner in the presence of poly(dA:dT). Furthermore, LvCypA also plays an important role in the regulation of the interferon system-like antiviral immunity in shrimp. The present results provide the first evidence to show that Cyclophilin A can modulate NLR-mediated cytokine-like antiviral immunity in animals. These findings shed light on the roles of NLRs in regulating host innate immunity, contributing valuable insights into this area of study.
NLRs对病毒核酸的细胞内识别以及随后抗病毒免疫的激活对于脊椎动物抵御病毒感染的宿主防御至关重要。然而，在无脊椎动物中，尤其是甲壳类动物，对这些过程的了解非常有限。在本研究中，在凡纳滨对虾中鉴定出一个属于NLRC亚家族的NLR基因（LvNLRC），并阐明了其在对DNA病毒的细胞内识别以及白斑综合征病毒（WSSV）感染期间抗病毒免疫中的功能。LvNLRC能够通过其富含亮氨酸的重复序列（LRR）结构域以剂量依赖的方式检测DNA病毒模拟物，如聚（dA:dT）。LRR结构域还识别WSSV编码VP24的部分DNA。LvNLRC可通过其NACHT结构域与LvSTING之间的直接相互作用来调节对虾中类似干扰素系统的抗病毒反应。与脊椎动物的调节机制不同，聚（dA:dT）的存在并不影响对虾中LvNLRC的NACHT结构域释放STING。有趣的是，在存在聚（dA:dT）的情况下，对虾亲环素A（LvCypA）可以以剂量依赖的方式直接与LvNLRC的NACHT结构域相互作用。此外，LvCypA在对虾中类似干扰素系统的抗病毒免疫调节中也起着重要作用。本研究结果首次证明亲环素A可以调节动物中NLR介导 的细胞因子样抗病毒免疫。这些发现揭示了NLRs在调节宿主固有免疫中的作用，为该研究领域提供了有价值的见解。
