IFIT3 inhibits Epstein‐Barr virus reactivation via upregulating innate immunity

• Published in: Journal of medical virology Vol. 95; no. 11; pp. e29237 - n/a
• Main Authors: Zhang, Wentao, Jiang, Mingjuan, Liao, Xuefei, Li, Yanling, Xin, Shuyu, Yang, Li, Xin, Yujie, Umar, Abdulrahim, Lu, Jianhong
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2023
• Subjects: Epithelial cells; Epithelium; Epstein-Barr virus; Epstein-Barr Virus Infections; Herpes viruses; Herpesvirus 4, Human; Homeostasis; Host-Pathogen Interactions; Humans; IFIT3; Immunity, Innate; Infections; Innate immunity; Interferon; Interferon regulatory factor 3; Interferons - metabolism; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Latent Infection; Lymphocytes; Lymphocytes B; lytic replication; Phosphorylation; Replication; Virology; Virus Activation; Virus Replication - physiology; Viruses; Epstein-Barr virus; innate immunity; latent infection; lytic replication; IFIT3
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.29237

Epstein‐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.