tetano
Editor, Senior Moderator
Am J Transl Res
. 2022 Nov 15;14(11):7689-7704.
eCollection 2022.
Inducible downregulation of miR-93 feedback promotes innate responses against RNA virus by amplifying interferon signaling
Yuanyu Zhao[SUP] 1 [/SUP], Fang Liu[SUP] 2 [/SUP], Junfeng Dong[SUP] 1 [/SUP], Hong Fu[SUP] 1 [/SUP], Jianhua Luo[SUP] 3 [/SUP], Junsong Ji[SUP] 1 [/SUP], Xiaogang Gao[SUP] 4 [/SUP], Wenyuan Guo[SUP] 1 [/SUP]
Affiliations
Abstract
Type I interferons (IFN) and their downstream effector signaling pathways play critical roles in the innate antiviral response. The underlying mechanisms that regulate IFN production and their effector signaling, especially by microRNAs, are well understood. We found that the expression of miR-93 was significantly downregulated by RNA virus infection in innate cells. miR-93 expression was also downregulated in influenza virus-infected patients. Furthermore, we showed that JAK1 is targeted by miR-93 to inhibit type I IFN's antiviral activity. Functionally, antagomir of miR-93 markedly reduced influenza virus replication in mice in vivo and prevented their death. Therefore, hosts recognize the invading RNA virus infection and activate RIG-I/JNK pathways to decrease miR-93 expression. The reduction of miR-93 feedback enhances the antiviral innate immune response by activating the IFN-JAK-STAT effectors type I, indicating miR-93 as a possible therapeutic target for infection with RNA viruses.
Keywords: IFN-JAK-STAT pathway; RNA virus; influenza A; innate immunity; microRNA; type I interferon.
. 2022 Nov 15;14(11):7689-7704.
eCollection 2022.
Inducible downregulation of miR-93 feedback promotes innate responses against RNA virus by amplifying interferon signaling
Yuanyu Zhao[SUP] 1 [/SUP], Fang Liu[SUP] 2 [/SUP], Junfeng Dong[SUP] 1 [/SUP], Hong Fu[SUP] 1 [/SUP], Jianhua Luo[SUP] 3 [/SUP], Junsong Ji[SUP] 1 [/SUP], Xiaogang Gao[SUP] 4 [/SUP], Wenyuan Guo[SUP] 1 [/SUP]
Affiliations
- PMID: 36505341
- PMCID: PMC9730083
Abstract
Type I interferons (IFN) and their downstream effector signaling pathways play critical roles in the innate antiviral response. The underlying mechanisms that regulate IFN production and their effector signaling, especially by microRNAs, are well understood. We found that the expression of miR-93 was significantly downregulated by RNA virus infection in innate cells. miR-93 expression was also downregulated in influenza virus-infected patients. Furthermore, we showed that JAK1 is targeted by miR-93 to inhibit type I IFN's antiviral activity. Functionally, antagomir of miR-93 markedly reduced influenza virus replication in mice in vivo and prevented their death. Therefore, hosts recognize the invading RNA virus infection and activate RIG-I/JNK pathways to decrease miR-93 expression. The reduction of miR-93 feedback enhances the antiviral innate immune response by activating the IFN-JAK-STAT effectors type I, indicating miR-93 as a possible therapeutic target for infection with RNA viruses.
Keywords: IFN-JAK-STAT pathway; RNA virus; influenza A; innate immunity; microRNA; type I interferon.