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Dengue Virus 2 NS2B Targets MAVS and IKKε to Evade the Antiviral Innate Immune Response
Nie Ying,Deng Dongqing,Mou Lumin,Long Qizhou,Chen Jinzhi,Wu Jiahong 한국미생물·생명공학회 2023 Journal of microbiology and biotechnology Vol.33 No.5
Dengue virus (DENV) is a widespread arbovirus. To efficiently establish infection, DENV evolves multiple strategies to hijack the host innate immune response. Herein, we examined the inhibitory effects of DENV serotype 2 (DENV2) nonstructural proteins on RIG-I-directed antiviral immune response. We found that DENV2 NS2A, NS2B, NS4A, and NS4B significantly inhibited RIG-I-mediated IFN-β promoter activation. The roles of NS2B in RIG-I-directed antiviral immune response are unknown. Our study further showed that NS2B could dose-dependently suppress RIG-I/MAVSinduced activation of IFN-β promoter. Consistently, NS2B significantly decreased RIG-I- and MAVSinduced transcription of IFNB1, ISG15, and ISG56. Mechanistically, NS2B was found to interact with MAVS and IKKε to impair RIG-I-directed antiviral response. Our findings demonstrated a previously uncharacterized function of NS2B in RIG-I-mediated antiviral response, making it a promising drug target for anti-DENV treatments.