Affiliation:
1. Department of Nuclear Medicine, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha Hunan China
2. Department of Microbiology, School of Basic Medical Science Central South University Changsha Hunan China
3. NHC Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute Central South University Changsha Hunan China
4. China‐Africa Research Center of Infectious Diseases Central South University Changsha Hunan China
Abstract
AbstractEpstein‐Barr virus (EBV), a member of the γ‐herpesvirus family, can establish latent infection in B lymphocytes and certain epithelial cells after primary infection. Under certain circumstances, EBV can enter into lytic replication. However, the regulation of EBV latent‐lytic infection remains largely unclear. The important immune molecule, interferon‐induced protein with tetratricopeptide repeats 3 (IFIT3), was upregulated in EBV latently infected cells. When the lytic replication of EBV was induced, the expression of IFIT3 was further increased. In turn, IFIT3 overexpression dramatically inhibited the lytic replication of EBV, while IFIT3 knockdown facilitated EBV lytic replication. Moreover, upon the lytic induction, the ectopic IFIT3 expression promoted the activation of the interferon (IFN) pathway, including the production of IFN‐stimulated genes (ISGs), IFNB1, and the phosphorylation of IFN‐regulatory factor 3 (IRF3). In contrast, the depletion of IFIT3 led to decreased ISGs and IFNB1 expression. Mechanically, IFIT3 inhibited EBV lytic replication through IFN signaling. This study revealed that the host innate immune‐related factor IFIT3 played an important role in regulating EBV latent‐lytic homeostasis. The results implied that EBV has evolved well to utilize host factors to maintain latent infection.
Subject
Infectious Diseases,Virology