title: HIST1H1C Regulates Interferon-β and Inhibits Influenza Virus Replication by Interacting with IRF3.
abstract: Influenza virus NS2 is well known for its role in viral ribonucleoprotein nuclear export; however, its function has not been fully understood. A recent study showed that NS2 might interact with HIST1H1C (H1C, H1.2). Histones have been found to affect influenza virus replication, such as the H2A, H2B, H3, and H4, but H1 has not been detected. Here, we found that H1C interacts with NS2viaits C-terminal in the nucleus and that H1C affects influenza virus replication. The H1N1 influenza virus replicates better in H1C knockout A549 cells compared to wild-type A549 cells, primarily because of the regulation of H1C on interferon-β (IFN-β). Further studies showed that the H1C phosphorylation mutant (T146A) decreases IFN-β, while H1C methylation mutants (K34A, K187A) increases IFN-β by releasing the nucleosome and promoting IRF3 binding to the IFN-β promoter. Interestingly, NS2 interacts with H1C, which reduces H1C-IRF3 interaction and results in the inhibition of IFN-β enhanced by H1C. In summary, our study reveals a novel function of H1C to regulate IFN-β and uncovers an underlying mechanism, which suggests H1C plays a role in epigenetic regulation. Moreover, our results suggest a novel mechanism for the influenza virus to antagonize the innate immune response by NS2.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University , Wuhan , China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University , Wuhan , China.
authors.forename: Cha
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; Hubei Collaborative Innovation Center for Industrial Fermentation, Hubei University of Technology, Wuhan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University , Wuhan , China.
authors.forename: Erming
authors.initials: E
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University , Wuhan , China.
authors.forename: Xian
authors.initials: X
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University , Wuhan , China.
authors.forename: Lianzhong
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University , Wuhan , China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; State Key Laboratory of Agricultural Microbiology, Key Laboratory of Agro-Microbiology Resources Development, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Anding
authors.initials: A
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; State Key Laboratory of Agricultural Microbiology, Key Laboratory of Agro-Microbiology Resources Development, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; State Key Laboratory of Agricultural Microbiology, Key Laboratory of Agro-Microbiology Resources Development, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; State Key Laboratory of Agricultural Microbiology, Key Laboratory of Agro-Microbiology Resources Development, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; State Key Laboratory of Agricultural Microbiology, Key Laboratory of Agro-Microbiology Resources Development, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Jin
keywords: HIST1H1C; IFN-β; IRF3; NS2; influenza A virus