Recently, the Waterfowl Virus Disease Innovation Team of Shanghai Veterinary Research Institute's found that non-structural protein V of Newcastle disease virus (NDV) recruits host E3 ubiquitin ligase RNF5 to degrade the important innate immune adaptor molecule MAVS, thereby inhibits hosts innate immunity to promote viral replication. This study reveals a novel mechanism by which NDV V protein antagonizes host innate immunity and is important for antiviral and anti-tumor therapies. The related research results were published online at July 3, 2019 in the Journal of Virology.

Virus infection activates a series of innate antiviral responses. Cytoplasmic RNA helicase is the most important cytoplasmic pattern recognition receptor for recognition of RNA viruses. Activation of mitochondrial antiviral signaling proteins (MAVS) induces innate immune pathways after recognition of viral nucleic acids. This study first proved that NDV infection induces MAVS degradation through the ubiquitin-proteasome pathway. NDV V protein inhibits IFN-β production by ubiquitination and degradation of MAVS. Further studies showed that V protein recruited E3 ubiquitin ligase RNF5 to degrade MAVS through 362 and 461 lysine targets. Compared with wild-type NDV, MAVS degradation in V-deficient NDV-infected cells were attenuated accompanied by the increased IFN-β production. Knockout of MAVS promoted wild-type NDV replication but had no effect on V-deficient NDV replication. Finally, this study demonstrates that similar to NDV, other paramyxovirus V proteins also degrades MAVS.
Paramyxovirus V protein antagonizes host innate immunity by various means. For example, their previous study showed that V protein degraded phosphorylated STAT1, the downstream molecules of IFN. Also, V protein inhibits innate immunity by interacting with MDA5. This study reveals that V protein can target MAVS for degradation to inhibit host innate immunity, which provide a theoretical basis for understanding the replication mechanism of NDV and other paramyxoviruses.
Yingjie Sun, the associate professor and Hang Zheng, the graduate student are the co-first authors of the paper. Chan Ding, the chief scientist of the Waterfowl Virus Disease Innovation Team, is the corresponding author. The research was funded by the National Natural Science Foundation of China and the Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences.

Paper link：https://jvi.asm.org/content/early/2019/06/27/JVI.00322-19.long