非特异性固有免疫是预防病毒感染的第一道防线,Toll样受体(toll-like receptors,TLRs)和维甲酸诱导基因I样受体(RIG-I like receptors,RLRs)是感知病毒RNA的两个主要受体家族。RLRs为存在于胞浆中的RNA解旋酶家族,可识别在病毒感染或复...非特异性固有免疫是预防病毒感染的第一道防线,Toll样受体(toll-like receptors,TLRs)和维甲酸诱导基因I样受体(RIG-I like receptors,RLRs)是感知病毒RNA的两个主要受体家族。RLRs为存在于胞浆中的RNA解旋酶家族,可识别在病毒感染或复制期间进入到胞浆内的单链或双链RNA。目前研究RLRs家族比较多的成员有维甲酸诱导型基因I(retinoic acid-inducible gene I,RIG-I)、黑色素瘤分化相关基因5(melanoma differentiation associated gene-5,MDA-5)及遗传学和生理学实验室蛋白2(laboratory of genetics and physiology 2,LGP2)。本文分别就RLRs家族中RIG-I和MDA-5结构、生物学作用及其信号传导中关键分子的研究进展作一概述。展开更多
Innate immunity is critical for the control of virus infection and operates to restrict viral susceptibility and direct antiviral immunity for protection from acute or chronic viral-associated diseases including cance...Innate immunity is critical for the control of virus infection and operates to restrict viral susceptibility and direct antiviral immunity for protection from acute or chronic viral-associated diseases including cancer. RIG-I like receptors(RLRs) are cytosolic RNA helicases that function as pathogen recognition receptors to detect RNA pathogen associated molecular patterns(PAMPs) of virus infection. The RLRs include RIG-I, MDA5, and LGP2. They function to recognize and bind to PAMP motifs within viral RNA in a process that directs the RLR to trigger downstream signaling cascades that induce innate immunity that controls viral replication and spread. Products of RLR signaling also serve to modulate the adaptive immune response to infection. Recent studies have additionally connected RLRs to signaling cascades that impart inflammatory and apoptotic responses to virus infection. Viral evasion of RLR signaling supports viral outgrowth and pathogenesis, including the onset of viral-associated cancer.展开更多
Pattern recognition receptors(PRRs) play important roles in innate immunity system and trigger the specific pathogen recognition by detecting the pathogen-associated molecular patterns. The main four PRRs components i...Pattern recognition receptors(PRRs) play important roles in innate immunity system and trigger the specific pathogen recognition by detecting the pathogen-associated molecular patterns. The main four PRRs components including Toll-like receptors(TLRs), RIG-I-like receptors(RLRs), NOD-like receptors(NLRs) and C-type lectin receptors(CLRs) were surveyed in the five genomes of non-teleost ray-finned fishes(NTR) including bichir(Polypterus senegalus), American paddlefish(Polyodon spathula), alligator gar(Atractosteus spatula), spotted gar(Lepisosteus oculatus) and bowfin(Amia calva), representing all the four major basal groups of ray-finned fishes. The result indicates that all the four PRRs components have been well established in these NTR fishes. In the RLR-MAVS signal pathway, which detects intracellular RNA ligands to induce production of type I interferons(IFNs), the MAVS was lost in bichir particularly. Also, the essential genes of recognition of Lipopolysaccharide(LPS) commonly in mammals like MD2, LY96 and LBP could not be identified in NTR fishes. It is speculated that TLR4 in NTR fishes may act as a cooperator with other PRRs and has a different pathway of recognizing LPS compared with that in mammals. In addition, we provide a survey of NLR and CLR in NTR fishes. The CLRs results suggest that Group V receptors are absent in fishes and Group II and VI receptors are well established in the early vertebrate evolution. Our comprehensive research of PRRs involving NTR fishes provides a new insight into PRR evolution in primitive vertebrate.展开更多
文摘非特异性固有免疫是预防病毒感染的第一道防线,Toll样受体(toll-like receptors,TLRs)和维甲酸诱导基因I样受体(RIG-I like receptors,RLRs)是感知病毒RNA的两个主要受体家族。RLRs为存在于胞浆中的RNA解旋酶家族,可识别在病毒感染或复制期间进入到胞浆内的单链或双链RNA。目前研究RLRs家族比较多的成员有维甲酸诱导型基因I(retinoic acid-inducible gene I,RIG-I)、黑色素瘤分化相关基因5(melanoma differentiation associated gene-5,MDA-5)及遗传学和生理学实验室蛋白2(laboratory of genetics and physiology 2,LGP2)。本文分别就RLRs家族中RIG-I和MDA-5结构、生物学作用及其信号传导中关键分子的研究进展作一概述。
基金supported by National Institutes of Health grants AI083019, AI104002, and AI88778
文摘Innate immunity is critical for the control of virus infection and operates to restrict viral susceptibility and direct antiviral immunity for protection from acute or chronic viral-associated diseases including cancer. RIG-I like receptors(RLRs) are cytosolic RNA helicases that function as pathogen recognition receptors to detect RNA pathogen associated molecular patterns(PAMPs) of virus infection. The RLRs include RIG-I, MDA5, and LGP2. They function to recognize and bind to PAMP motifs within viral RNA in a process that directs the RLR to trigger downstream signaling cascades that induce innate immunity that controls viral replication and spread. Products of RLR signaling also serve to modulate the adaptive immune response to infection. Recent studies have additionally connected RLRs to signaling cascades that impart inflammatory and apoptotic responses to virus infection. Viral evasion of RLR signaling supports viral outgrowth and pathogenesis, including the onset of viral-associated cancer.
基金supported by the National Natural Science Foundation of China(31372190)
文摘Pattern recognition receptors(PRRs) play important roles in innate immunity system and trigger the specific pathogen recognition by detecting the pathogen-associated molecular patterns. The main four PRRs components including Toll-like receptors(TLRs), RIG-I-like receptors(RLRs), NOD-like receptors(NLRs) and C-type lectin receptors(CLRs) were surveyed in the five genomes of non-teleost ray-finned fishes(NTR) including bichir(Polypterus senegalus), American paddlefish(Polyodon spathula), alligator gar(Atractosteus spatula), spotted gar(Lepisosteus oculatus) and bowfin(Amia calva), representing all the four major basal groups of ray-finned fishes. The result indicates that all the four PRRs components have been well established in these NTR fishes. In the RLR-MAVS signal pathway, which detects intracellular RNA ligands to induce production of type I interferons(IFNs), the MAVS was lost in bichir particularly. Also, the essential genes of recognition of Lipopolysaccharide(LPS) commonly in mammals like MD2, LY96 and LBP could not be identified in NTR fishes. It is speculated that TLR4 in NTR fishes may act as a cooperator with other PRRs and has a different pathway of recognizing LPS compared with that in mammals. In addition, we provide a survey of NLR and CLR in NTR fishes. The CLRs results suggest that Group V receptors are absent in fishes and Group II and VI receptors are well established in the early vertebrate evolution. Our comprehensive research of PRRs involving NTR fishes provides a new insight into PRR evolution in primitive vertebrate.