Biology subjects

Wang, y.

Publications and source records attributed to Wang, y..

3 recordsLinked to original sources

bioRxiv2024

Env from EIAV vaccine delicately regulates NLRP3 activation via attenuating NLRP3-NEK7 interaction

The current equine infectious anemia virus (EIAV) vaccine causes attenuation of the inflammatory response to an appropriate level, compared to that produced by virulent EIAV. However, how the EIAV vaccine finely regulates the inflammatory response remains unclear. Using a constructed NLRP3-IL-1{beta} screening system, viral proteins from two EIAV strains (the attenuated vaccine and its virulent mother strain) were examined separately. Firstly, EIAV-Env was screened to direct binding P2X7(R) with notable K+ efflux trans-cellularly. Secondly, EIAV-Env was found to bind NLRP3 and/or NEK7 to trigger aggregation of NLRP3-NEK7 to form NLRP3-NEK7 complex in cells. Comparison of the two strains, we observed a significant reduction on vaccine-Env-initiated NLRP3-NEK7 complex formation, with no difference in Env triggering P2X7(R)-mediated ion fluxes. Thirdly, reciprocally mutation on four stable varied amino acids between two strains produced an anticipated outcome on NLRP3-IL-1{beta}-axis activation. As the attenuated vaccine was shown evolved as a natural quasispecies of the virulent EIAV, its precise and adaptable regulation via spatial proximity-dependent intracellular activation might present a "win-win" virus-host adaption, offering an alternative strategy on HIV vaccine development. Author SummaryHere, we report that EIAV-Env mediates NLRP3 inflammasome activation through two distinct pathways. The first pathway involves a transcellular mechanism driven by K+ flux, which couples Env-P2X7 interaction. The second pathway entails direct intracellular binding between Env and NLRP3, promoting the assembly of NLRP3-NEK7 and subsequent inflammasome formation. Notably, we observed a marked difference in NLRP3 inflammasome activation between the vaccine and virulent strains, which was reflected in the extent of Env-mediated NLRP3-NEK7 aggregation. This study not only enhances our understanding of lentivirus-host immune interactions but also contributes to the broader discourse on virus evolution and host-induced inflammation.

immunology↗

bioRxiv2024

Comparative genomics illuminates adaptive evolution of DVNP with lifestyle and with loss of histone H1 in dinoflagellates

About ten years ago dinoflagellate/viral nucleoprotein (DVNP) was discovered in dinoflagellates, an ecologically important and evolutionarily enigmatic group of aquatic protists. Apparently acquired from a viral origin, the appearance of DVNP coincided with the loss of nucleosome, a rare event in eukaryote evolution. Despite the potential importance of DVNP as the substitute of histones, its evolutionary trajectory and adaptive significance remain elusive. Here, we conducted comparative analyses using existing dinoflagellate genomes and transcriptomes from 26 species ranging from ancestral to later-diverging lineages to investigate the pattern of sequence and structural divergence. Results showed that the functional domestication of DVNP in ancestral dinoflagellates coincided with the loss of histone H1, while subsequent DVNP differentiation was accompanied by the yet another genomic innovation: acquisition of bacterial-originated histone-like protein. Furthermore, our data split DVNP into two major groups: the core DVNP that resembles histone H1 and shows consistently high levels of expression and the non-core DVNP with higher sequence variability and showing lower yet variable levels of expression. In addition, we observed a trend in DVNP evolution tracing that in lifestyle differentiation. This work offers insights into the adaptive evolution of DVNP, laying the foundation for further inquiries of evolutionary drivers and functional innovation of DVNP to enhance our understanding of dinoflagellate evolution and ecological success.

microbiology↗

bioRxiv2023

Exposure to titanium dioxide nanoparticles accelerates abnormal fat deposition through the mediation of the ROS via the AGE-RAGE signaling pathway in mice

Titanium dioxide nanoparticles (TiO2 NPs) are widely added to various types of foods as food additives. Previous studies have shown that TiO2 NPs exposure can cause abnormal deposition of adipose tissue in organisms, resulting in lipid metabolism disorder. However, the potential molecular mechanisms underlying TiO2 NPs effects have yet to be elucidated. In this study, our data indicated that TiO2 NPs (100 mg/Kg BW, 20 nm) accelerated abnormal fat deposition in the epididymal adipose tissues and disturbed the level of blood glucose subsequently in normal-fat diet mice. Further studies showed that TiO2 NPs at a concentration of 100 {micro}g/mL significantly induced the proliferation and differentiation of 3T3-L1 preadipocytes. Mechanistic studies we revealed that TiO2 NPs induced the overproduction of reactive oxygen species (ROS) in the cytoplasm, which subsequently upregulated the expression of receptors for advanced glycation end products (AGEs) leading to lipid accumulation in the adipocytes with a higher level of ROS. However, the antioxidant N-acetylcysteine (NAC) was a therapeutic potential for lipid overaccumulation in the adipocytes. This study provides insight into the mechanism underlying fat deposition induced by TiO2 NPs and highlighted the need for reevaluation of food-grade TiO2 NPs exposure in daily life.

cell biology↗