Epigenetic Modification Is Regulated by the Interaction of Influenza A Virus Nonstructural Protein 1 with the De Novo DNA Methyltransferase DNMT3B and Subsequent Transport to the Cytoplasm for K48-Linked Polyubiquitination

作者：Shi Liu, Li Liu, Gang Xu, Zhongying Cao, Qing Wang, Shun Li, Nanfang Peng, Jingchuan Yin, Haisheng Yu, Mengqi Li, Zhangchuan Xia, Li Zhou, Yong Lin, Xueyu Wang, Qian Li, Chengliang Zhu, Xuecheng Yang, Jun Wang, Yinglong She, Mengji Lu, Ying Zhu · 发表于：Journal of Virology · 年份：2019 · DOI：10.1128/jvi.01587-18 · 被引用次数：36 · 研究领域：Influenza Virus Research Studies、Epigenetics and DNA Methylation、RNA modifications and cancer

The nonstructural protein 1 (NS1) of the influenza A virus (IAV) is a multifunctional protein that counters cellular antiviral activities and is a virulence factor. However, the involvement of NS1 in DNA methylation during IAV infection has not been established. Here, we reveal that the NS1 protein binds the cellular DNMT3B DNA methyltransferase, thereby inhibiting the methylation of the promoters of genes encoding suppressors of JAK-STAT signaling. As a result, these suppressor genes are induced, and JAK-STAT signaling is inhibited. Furthermore, we demonstrate that the NS1 protein transports DNMT3B to the cytoplasm for ubiquitination and degradation. Thus, we identify the NS1 protein as a potential trigger of the epigenetic deregulation of JAK-STAT signaling suppressors and illustrate a novel mechanism underlying the regulation of host immunity during IAV infection.