title: Influenza a virus NS1 protein induced A20 contributes to viral replication by suppressing interferon-induced antiviral response.
abstract: The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. A20 is a cytoplasmic ubiquitin-editing protein that negatively regulates the retinoic acid-inducible gene I (RIG-I)-mediated activation of interferon regulatory factors (IRF) 3. Here, we found that influenza A virus (IAV) non-structural protein (NS) 1 dramatically induced the protein level of A20 in A549 cells whose expression levels were positively associated with the viral virulence. A20 overexpression in A549 cells significantly suppressed IAV-induced the activation of IRF3 and interferon (IFN) promoter, resulted in downregulation of IFNβ and IFN-stimulated genes (ISGs) mRNA. Conversely, silencing A20 expression markedly enhanced IRF3-mediated innate antiviral responses. Furthermore, we demonstrated that A20 overexpression in A549 cells obviously promoted IAV replication, and conversely, knockdown of A20 inhibited the viral replication. Overall, the findings described in this study support and extend previous results on interferon-antagonistic strategies of IAV NS1 by showing an induced host target A20, which restricts IAV-induced host innate immune antiviral responses and thereby facilitates viral replication.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Feng
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute of Special Economic Animal and Plant Sciences, Chinese Academy of Agricultural Sciences CAAS, Changchun 132109, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Shi
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China.
authors.forename: Maolin
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China.
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Guan
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China. Electronic address: duan_ming@jlu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Duan
mesh_terms: D000072283:A549 Cells; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D004285:Dogs; D020868:Gene Silencing; D006801:Humans; D007113:Immunity, Innate; D009980:Influenza A virus / Q000502:physiology*; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C085820:INS1 protein, influenza virus; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
keywords: A20; Influenza A virus; NS1; Viral replication