In late 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged in Wuhan, China. SARS‐CoV‐2 and the disease it causes, coronavirus disease 2019 (COVID‐19), spread rapidly and became a global pandemic in early 2020. SARS‐CoV‐2 spike protein is responsible for viral entry and binds to angiotensin converting enzyme 2 (ACE2) on host cells, making it a major target of the immune system – particularly neutralizing antibodies (nAbs) that are induced by infection or vaccines. Extracellular vesicles (EVs) are small membraned particles constitutively released by cells, including virally‐infected cells. EVs and viruses enclosed within lipid membranes share some characteristics: they are small, sub‐micron particles and they overlap in cellular biogenesis and egress routes. Given their shared characteristics, we hypothesized that EVs released from spike‐expressing cells could carry spike and serve as decoys for anti‐spike nAbs, promoting viral infection. Here, using mass spectrometry and nanoscale flow cytometry (NFC) approaches, we demonstrate that SARS‐CoV‐2 spike protein can be incorporated into EVs. Furthermore, we show that spike‐carrying EVs act as decoy targets for convalescent patient serum‐derived nAbs, reducing their effectiveness in blocking viral entry. These findings have important implications for the pathogenesis of SARS‐CoV‐2 infection in vivo and highlight the complex interplay between viruses, extracellular vesicles, and the immune system that occurs during viral infections.
Over the past three decades the United States has experienced a devastating opioid epidemic. One of the many debilitating side effects of chronic opioid use is opioid-induced bowel dysfunction. We investigated the impact of methadone maintenance treatment (MMT) on the gut microbiome, the gut bacterial metabolite profile, and intestinal barrier integrity. An imbalance in key bacterial communities required for production of short-chain fatty acids (SCFAs), mucus degradation, and maintenance of barrier integrity was identified. Consistent with dysbiosis, levels of fecal SCFAs were reduced in MMT. We demonstrated that metabolites synthesized by Akkermansia muciniphila modulate intestinal barrier integrity in vitro by strengthening the pore pathway and regulating tight junction protein expression. This study provides essential information about the therapeutic potential of A. muciniphila and warrants development of new clinical strategies that aim to normalize the gut microbiome in individuals affected by chronic opioid use.
At present, it is generally acknowledged that EVs are secreted by almost all living cells including plant cells. [4] Compared with mammalian EVs, the research of plant EVs is still in its infancy. Increasing evidence has proved that plant cells are able to secret exosome-like vesicles or extracellular vesicles into apoplast space. [5] In the 1960s, using transmission electron microscopy (TEM), Halperin et al. for the first time observed and discovered multivesicular bodies (MVBs) fusing with the plasma membrane and releasing exosome-like vesicles into the cell wall area in carrot cell cultures. [6] Fifty years after this first discovery, Regenteet al. used a tissue-infiltration-centrifugation method and successfully separated exosome-like vesicles from apoplast washing fluids (AWF) of sunflower seeds. [5a] Following these discoveries, plant exosomelike vesicles or vesicle-like nanoparticles have been successfully isolated from many plant species, including ginseng, ginger, broccoli, bitter melon, oat, grape, grapefruit, lemon, blueberry, orange, sunflower seed, and Arabidopsis, etc. [5a,7] The efficient separation of PDVLNs from plant cells is still one of the challenges that need to be solved in the plant EV field. At present, two plant tissue pre-processing methods, namely tissue-disruption and tissue-infiltration centrifugation, have emerged as favorite methods used for vesicle separation from plant cells in the field. [5b,8] After tissue pre-treatment, most studies use ultracentrifugation or density gradient centrifugation for further PDVLN separation. [5a,9] In addition, novel separation methods are under development for PDVLNs, such as ultrafiltration, immunoaffinity capture, size-exclusive chromatography, etc. [5b,7j,10] However, it is still challenging to isolate specific PDVLN subtypes, due to the lack of generic or specific markers for PDVLNs and well-verified plant species antibodies. [4b,5b] The nomenclature of vesicles prepared by these methods is not standardized in existing references. Many terms were used, including "plant particles", "plant vesicles", etc. [7b,8b,10,11] To facilitate communication in the plant vesicle field, standardizing the nomenclatures is necessary. We thus propose to unify these nomenclatures into plant-derived vesicle-like nanoparticles (PDVLNs) in this review.PDVLNs share many similar physical characteristics to those of human-derived EVs, including features such as morphology, particle size, concentration, Zeta potential, etc. [2a,7b,e,11] To further elucidate the specific molecular mechanism of PDVLNs on Extracellular vesicles (EVs) are heterogeneous, phospholipid bilayer-enclosed biological particles that regulate cell communication by molecular cargo delivery and surface signaling. EVs are secreted by almost all living cells, including plant cells. Plant-derived vesicle-like nanoparticles (PDVLNs) is a generic term referring to vesicle-like nanostructure particles isolated from plants. Their low immunogenicity and wide availability make PDVLNs safer and mor...
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