The matrix protein of Newcastle disease virus inhibits inflammatory response through IRAK4/TRAF6/TAK1/NF-κB signaling pathway.

The matrix (M) protein of several cytoplasmic RNA viruses has been reported to be an NF-κB pathway antagonist. However, the function and mechanism of NDV M protein antagonizing NF-κB activation remain largely unknown. In this study, we found that the expression levels of IRAK4, TRAF6, TAK1, and RELA/p65 were obviously reduced late in NDV infection. In addition, the cytoplasmic M protein rather than other viral proteins decreased the expression of these proteins in a dose-dependent manner. Further indepth analysis showed that the N-terminal 180 amino acids of M protein were not only responsible for the reduced expression of these proteins, but also responsible for the inhibition of NF-κB activation and nuclear translocation of RELA/p65, as well as the production of inflammatory cytokines. Moreover, small interference RNA-mediated knockdown of IRAK4 or overexpression of IRAK4 markedly enhanced or reduced NDV replication by decreasing or increasing inflammatory cytokines production through the IRAK4/TRAF6/TAK1/NF-κB signaling pathway. Strangely, there were no interactions detected between NDV M protein and IRAK4, TRAF6, TAK1 or RELA/p65. Our findings described here contribute to a better understanding of the innate immune antagonism function of M protein and the molecular mechanism underlying the replication and pathogenesis of NDV.

Enhanced Detection in Droplet Microfluidics by Acoustic Vortex Modulation of Particle Rings and Particle Clusters via Asymmetric Propagation of Surface Acoustic Waves.

As a basis for biometric and chemical analysis, issues of how to dilute or concentrate substances such as particles or cells to specific concentrations have long been of interest to researchers. In this study, travelling surface acoustic wave (TSAW)-based devices with three frequencies (99.1, 48.8, 20.4 MHz) have been used to capture the suspended Polystyrene (PS) microspheres of various sizes (5, 20, 40 µm) in sessile droplets, which are controlled by acoustic field-induced fluid vortex (acoustic vortex) and aggregate into clusters or rings with particles. These phenomena can be explained by the interaction of three forces, which are drag force caused by ASF, ARF caused by Leaky-SAW and varying centrifugal force. Eventually, a novel approach of free transition between the particle ring and cluster was approached via modulating the acoustic amplitude of TSAW. By this method, multilayer particles agglomerate with 20 µm wrapped around 40 µm and 20 µm wrapped around 5 µm can be obtained, which provides the possibility to dilute or concentrate the particles to a specific concentration.

Influence of Structural Parameters on Performance of SAW Resonators Based on 128° YX LiNbO3 Single Crystal.

The seeking of resonator with high Q and low insertion loss is attractive for critical sensing scenes based on the surface acoustic wave (SAW). In this work, 128° YX LiNbO3-based SAW resonators were utilized to optimize the output performance through IDT structure parameters. Once the pairs of IDTs, the acoustic aperture, the reflecting grid logarithm, and the gap between IDT and reflector are changed, a better resonance frequency of 224.85 MHz and a high Q of 1364.5 were obtained. All the results demonstrate the structure parameters design is helpful for the performance enhancement with regard to SAW resonators, especially for designing and fabricating high-Q devices.

High-Performance Piezoelectric-Type MEMS Vibration Sensor Based on LiNbO3 Single-Crystal Cantilever Beams.

It is a great challenge to detect in-situ high-frequency vibration signals for extreme environment applications. A highly sensitive and robust vibration sensor is desired. Among the many piezoelectric materials, single-crystal lithium niobate (LiNbO3) could be a good candidate to meet the demand. In this work, a novel type of micro-electro-mechanical system (MEMS) vibration sensor based on a single crystalline LiNbO3 thin film is demonstrated. Firstly, the four-cantilever-beam MEMS vibration sensor was designed and optimized with the parametric method. The structural dependence on the intrinsic frequency and maximum stress was obtained. Then, the vibration sensor was fabricated using standard MEMS processes. The practical intrinsic frequency of the as-presented vibration sensor was 5.175 kHz, which was close to the calculated and simulated frequency. The dynamic performance of the vibration sensor was tested on a vibration platform after the packaging of the printed circuit board. The effect of acceleration was investigated, and it was observed that the output charge was proportional to the amplitude of the acceleration. As the loading acceleration amplitude is 10 g and the frequency is in the range of 20 to 2400 Hz, the output charge amplitude basically remains stable for the frequency range from 100 Hz to 1400 Hz, but there is a dramatic decrease around 1400 to 2200 Hz, and then it increases significantly. This should be attributed to the significant variation of the damping coefficient near 1800 Hz. Meanwhile, the effect of the temperature on the output was studied. The results show the nearly linear dependence of the output charge on the temperature. The presented MEMS vibration sensors were endowed with a high output performance, linear dependence and stable sensitivity, and could find potential applications for the detection of wide-band high-frequency vibration.

The association of ribosomal protein L18 with Newcastle disease virus matrix protein enhances viral translation and replication.

Numerous studies have shown that viruses can utilize or manipulate ribosomal proteins to achieve viral protein biosynthesis and replication. In our recent studies using proteomics analysis of virus-infected cells, we found that ribosomal protein L18 (RPL18) was the highest up-regulated differentially expressed protein, along with the increasingly expressed viral proteins later in Newcastle disease virus (NDV) infection. However, the association of RPL18 with viral protein biosynthesis and NDV replication remains unclear. In this study, we found that the expression and transcription levels of RPL18 was reduced early in NDV infection but increased later in NDV infection. In addition, the presence of cytoplasmic NDV matrix (M) protein was responsible for the increased expression of RPL18 in both virus-infected cells and plasmid-transfected cells. Moreover, cytoplasmic M protein increased RPL18 expression in a dose-dependent manner, even though they did not interact with each other. Furthermore, siRNA-mediated knockdown of RPL18 or overexpression of RPL18 dramatically reduced or enhanced NDV replication by decreasing or increasing viral protein translation rather than viral RNA synthesis and transcription. Taken together, these results suggested that the increased expression of RPL18 might be associated with the physical clumping together of the M protein, which in turn promoted viral protein biosynthesis and NDV replication. RESEARCH HIGHLIGHTSThe increased expression of RPL18 is associated with the presence of cytoplasmic M protein.Cytoplasmic M protein increases RPL18 expression in a dose-dependent manner.Knockdown of RPL18 reduces NDV replication by decreasing viral protein translation.Overexpression of RPL18 enhances NDV replication by increasing viral protein translation.

Chicken bromodomain-containing protein 2 interacts with the Newcastle disease virus matrix protein and promotes viral replication.

Bromodomain-containing protein 2 (BRD2) is a nucleus-localized serine-threonine kinase that plays pivotal roles in the transcriptional control of diverse genes. In our previous study, the chicken BRD2 (chBRD2) protein was found to interact with the Newcastle disease virus (NDV) matrix (M) protein using a yeast two-hybrid screening system, but the role of the chBRD2 protein in the replication of NDV remains unclear. In this study, we first confirmed the interaction between the M protein and chBRD2 protein using fluorescence co-localization, co-immunoprecipitation and pull-down assays. Intracellular binding studies indicated that the C-terminus (aa 264-313) of the M protein and the extra-terminal (ET) domain (aa 619-683) of the chBRD2 protein were responsible for interactions with each other. Interestingly, although two amino acids (T621 and S649) found in the chBRD2/ET domain were different from those in the human BRD2/ET domain and in that of other mammals, they did not disrupt the BRD2-M interaction or the chBRD2-M interaction. In addition, we found that the transcription of the chBRD2 gene was obviously decreased in both NDV-infected cells and pEGFP-M-transfected cells in a dose-dependent manner. Moreover, small interfering RNA-mediated knockdown of chBRD2 or overexpression of chBRD2 remarkably enhanced or reduced NDV replication by upregulating or downregulating viral RNA synthesis and transcription, respectively. Overall, we demonstrate for the first time that the interaction of the M protein with the chBRD2 protein in the nucleus promotes NDV replication by downregulating chBRD2 expression and facilitating viral RNA synthesis and transcription. These results will provide further insight into the biological functions of the M protein in the replication of NDV.