DEAD/DEAH-box helicase 5 is hijacked by an avian oncogenic herpesvirus to inhibit interferon beta production and promote viral replication. (June 2021)

• Record Type: Journal Article
• Authors: Xu, Jian; Cai, Yunhong; Ma, Zhenbang; Jiang, Bo; Liu, Wenxiao; Cheng, Jing; Jin, Huan; Li, Yongqing
• Is Part Of: Developmental and comparative immunology. Volume 119(2021)
• Publication Date: 2021-06
• Subjects: Avian oncogenic herpesvirus -- DEAD-box helicase 5 -- Interferon beta -- Interferon regulatory factor 1 -- MDA5/TLR3 signaling; Immunology -- Periodicals; Developmental immunology -- Periodicals; 616.079
• DOI: 10.1016/j.dci.2021.104048
• Languages: English
• ISSNs: 0145-305X

Abstract

Abstract: DEAD-box helicase 5 (DDX5) plays a significant role in tumorigenesis and regulates viral replication of several viruses. An avian oncogenic herpesvirus, Marek's disease virus (MDV), is widely known to cause immunosuppression and lymphoma in chickens. However, the underlying mechanisms of how DDX5 plays a role in viral replication remain unclear. In this study, we show that MDV inhibits the production of interferon beta (IFN-β) in chicken embryo fibroblasts (CEFs) by increasing the expression level and promoting the nuclear aggregation of DDX5. We further reveal how DDX5 down-regulates melanoma differentiation-associated gene 5/toll-like receptor 3 signaling through the fundamental transcription factor, interferon regulatory factor 1. MDV replication is suppressed, and the production of IFN-β is promoted in the DDX5 absented CEFs. Taken together, our investigations demonstrate that MDV inhibits IFN-β production by targeting DDX5-mediated signaling to facilitate viral replication, which offers a novel insight into the mechanism by which an avian oncogenic herpesvirus replicates in chicken cells. Highlights: Marek's disease virus increased the expression and nuclear aggregation of DDX5. DDX5 was identified as a negative regulator of IFN-β production in chicken cells. DDX5 blocked MDA5/TLR3 signaling via transcription factor IRF1. Marek's disease virus utilized DDX5 to promote viral replication in chicken cells.