Paramyxovirus establishes an intimate and complex interaction with the host cell to counteract the antiviral responses elicited by the cell. Of the various pattern recognition receptors in the host, the cytosolic RNA helicases interact with viral RNA to activate the mitochondrial antiviral signaling protein (MAVS) and subsequent cellular interferon (IFN) response. On the other hand, viruses explore multiple strategies to resist host immunity. In this study, we found that Newcastle disease virus (NDV) infection induced MAVS degradation. Further analysis showed that NDV V protein degraded MAVS through the ubiquitin-proteasome pathway to inhibit IFN-␤ production. Moreover, NDV V protein led to proteasomal degradation of MAVS through Lys362 and Lys461 ubiquitin to prevent IFN production. Further studies showed that NDV V protein recruited E3 ubiquitin ligase RNF5 to polyubiquitinate and degrade MAVS. Compared with levels for wild-type NDV infection, V-deficient NDV induced attenuated MAVS degradation and enhanced IFN-␤ production at the late stage of infection. Several other paramyxovirus V proteins showed activities of degrading MAVS and blocking IFN production similar to those of NDV V protein. The present study revealed a novel role of NDV V protein in targeting MAVS to inhibit cellular IFN production, which reinforces the fact that the virus orchestrates the cellular antiviral response to its own benefit. IMPORTANCE Host anti-RNA virus innate immunity relies mainly on the recognition by retinoic acid-inducible gene I and melanoma differentiation-associated protein 5 and subsequently initiates downstream signaling through interaction with MAVS. On the other hand, viruses have developed various strategies to counteract MAVSmediated signaling. The mechanism for paramyxoviruses regulating MAVS to benefit their infection remains unknown. In this article, we demonstrate that the V proteins of NDV and several other paramyxoviruses target MAVS for ubiquitin-mediated degradation through E3 ubiquitin ligase RING-finger protein 5 (RNF5). MAVS degradation leads to the inhibition of the downstream IFN-␤ pathway and therefore benefits virus proliferation. Our study reveals a novel mechanism of NDV evading host innate immunity and provides insight into the therapeutic strategies for the control of paramyxovirus infection.

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A 42-day experiment was conducted with 625 1-day-old male Hubbard chickens to evaluate the performance, carcass traits, nitrogen retention and economics of broiler chickens fed low protein and amino acid diets supplemented with different protease sources. Treatments included positive (PC) and negative (NC) controls (PC at 19.3% protein vs NC at 18.8% protein), with NC containing 7% less digestible amino acids. The other three treatment groups were based on the NC diet supplemented with 0.05% Cibenza® DP100 (CB), 0.02% Ronozyme® (RZ) or 0.02% Winzyme pro plus (WZ). Birds fed the PC, CB and WZ diets achieved the heaviest bodyweight compared with those fed the NC diet at end of the experiment. Total feed intake of birds fed the PC diet was higher (P < 0.05) than that of birds fed the NC diet. Feed conversion ratio was numerically significantly (P = 0.005) improved with all tested groups in comparison with NC throughout the experiment. European production index was similar (P > 0.05) among birds fed the PC, NC, RZ or WZ diets. All carcass parameters studied, including dressing, heart, gizzard, giblets, chest meat, thigh meat and abdominal fat percentages, were not significantly (P > 0.05) affected by feeding on the different sources of protease. Broilers fed the PC diet or diets formulated with all protease sources had higher (P < 0.05) nitrogen retention than did birds fed the NC diet. The supplementation of protease to low-protein and low-amino acid diets resulted in higher profit margin in broilers. It is concluded that supplementing exogenous protease to broiler diets containing low protein and amino acids improved the growth performance, feed utilisation, carcass traits, nitrogen retention and net returns of broiler chickens.