Retinoic acid-inducible gene I(RIG-l)-like receptors(RLRs)are RNA sensor molecules that play essential roles in innate antiviral immunity.Among the three RLRs encoded by the human genome,RIG-1 and melanoma differentia...Retinoic acid-inducible gene I(RIG-l)-like receptors(RLRs)are RNA sensor molecules that play essential roles in innate antiviral immunity.Among the three RLRs encoded by the human genome,RIG-1 and melanoma differentiation-associated gene 5,which contain N-terminal caspase recruitment domains,are activated upon the detection of viral RNAs in the cytoplasm of virus-infected cells.Activated RLRs induce downstream signaling via their interactions with mitochondrial antiviral signaling proteins and activate the production of type Ⅰ and Ⅲ interferons and inflammatory cytokines.Recent studies have shown that RLR-mediated signaling is regulated by interactions with endogenous RNAs and host proteins,such as those involved in stress responses and posttranslational modifications.Since RLR-mediated cytokine production is also involved in the regulation of acquired immunity,the deregulation of RLR-mediated signaling is associated with autoimmune and autoinflammatory disorders.Moreover,RLRmediated signaling might be involved in the aberrant cytokine production observed in coronavirus disease 2019.Since the discovery of RLRs in 2004,significant progress has been made in understanding the mechanisms underlying the activation and regulation of RLR-mediated signaling pathways.Here,we review the recent advances in the understanding of regulated RNA recognition and signal activation by RLRs,focusing on the interactions between various host and viral factors.展开更多
基金supported by Grants-in-Aids for Scientific Research(B)(18H02660)and(Q(19K07589 and 20K07534)from the Ministry of Education,Culture,Sports,Science,and Technology of Japan。
文摘Retinoic acid-inducible gene I(RIG-l)-like receptors(RLRs)are RNA sensor molecules that play essential roles in innate antiviral immunity.Among the three RLRs encoded by the human genome,RIG-1 and melanoma differentiation-associated gene 5,which contain N-terminal caspase recruitment domains,are activated upon the detection of viral RNAs in the cytoplasm of virus-infected cells.Activated RLRs induce downstream signaling via their interactions with mitochondrial antiviral signaling proteins and activate the production of type Ⅰ and Ⅲ interferons and inflammatory cytokines.Recent studies have shown that RLR-mediated signaling is regulated by interactions with endogenous RNAs and host proteins,such as those involved in stress responses and posttranslational modifications.Since RLR-mediated cytokine production is also involved in the regulation of acquired immunity,the deregulation of RLR-mediated signaling is associated with autoimmune and autoinflammatory disorders.Moreover,RLRmediated signaling might be involved in the aberrant cytokine production observed in coronavirus disease 2019.Since the discovery of RLRs in 2004,significant progress has been made in understanding the mechanisms underlying the activation and regulation of RLR-mediated signaling pathways.Here,we review the recent advances in the understanding of regulated RNA recognition and signal activation by RLRs,focusing on the interactions between various host and viral factors.
