Studies have revealed a new mechanism by which duck tambusu virus uses host regulation of interferon

Recently, the team of Professor Jia Renyong of the College of Veterinary Medicine of Sichuan Agricultural University published two research papers entitled “Duck Tambusu Virus Inhibits Type I Interferon Production through JOSD1-SOCS1-IRF7 Negative Feedback Regulation Pathway” and “RNF123 Mediates Ubiquitination and Degradation of SOCS1 to Regulate Type I Interferon Production During Duck Tambusu Virus Infection”, respectively, in the Journal of Virology. The latest research results of duck tambusu virus (DTMUV) using SOCS1 protein to regulate interferon type I (IFN) signaling were reported for the first time, which provided an important theoretical basis for the effective prevention and control of this disease.

DTMUV belongs to the genus of flaviviruses in the flaviviridae family, which mainly causes damage to the immune organs of waterfowl, neurological dysfunction and decreased egg production, often causing serious economic losses to the waterfowl industry. The study found that the pre-infection of DTMUV made the virus unaffected by late IFN treatment, but the antiviral effect of DTMUV inhibiting type I IFN is not clear, and the reason for the upregulation of SOCS1 during DTMUV infection has not been clarified.

This study elucidates that the activation of TLR3 signaling pathway promotes the expression of SOCS1 during DTMUV infection, and the upregulated SOCS1 promotes DTMUV replication by mediating ubiquitination and proteasome degradation of K48 linkage of IRF7. Further studies have found that SOCS1 protein itself has K48-linked ubiquitination modification, JOSD1 as a deubiquitinase mediates SOCS1 deubiquitination to stabilize the expression of SOCS1, and JOSD1 inhibits the production of type I IFN during DTMUV infection by stabilizing the expression of SOCS1.

Photo courtesy of Sichuan Agricultural University

Although the above studies illustrate the upregulation mechanism of SOCS1 during DTMUV infection, it has been confirmed which E3 ubiquitin ligase mediates the ubiquitination of SOCS1. After further in-depth research, the research team found that RNF123, as an E3 ubiquitin ligase, binds to the SH2 domain of SOCS1 through its RING domain, promotes K48-linked ubiquitination of K114 and K137 sites of SOCS1 and proteasome degradation of SOCS1, and ultimately promotes TLR3/IRF7-induced type I IFN expression and inhibits viral replication.

This study systematically reveals a new mechanism by which viruses use SOCS1 protein to regulate type I IFN signaling during DTMUV infection, reveals for the first time that E3 ubiquitin ligase RNF123 mediates K48-linked ubiquitination of SOCS1, and also provides an important theoretical basis for clarifying whether other flaviviruses use SOCS1 protein to inhibit type I IFN signaling, and also provides possible targets for clinical vaccine development and new ideas for effective prevention and control of viral infection.

Huang Shanzhi, a 2020 doctoral student in preventive veterinary medicine at Sichuan Agricultural University, is the first author of the two papers, and Cheng Anchun and Jia Renyong, professors of the College of Veterinary Medicine of Sichuan Agricultural University, are co-corresponding authors. The research was supported by the National Natural Science Foundation of China and the Natural Science Foundation of Sichuan Province. (Source: Zhang Qingdan, China Science News)

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