Bombyx mori Nucleopolyhedrovirus Hijacks Multivesicular Body as an Alternative Envelopment Platform for Budded Virus Egress.

Baculovirus budded virus (BV) acquires its envelope and viral membrane fusion proteins from the plasma membrane (PM) of the host cell during the budding process. However, this classical BV egress pathway has been questioned because an intracellularly localized membrane fusion protein, SPΔnGP64 (glycoprotein 64 [GP64] lacking the signal peptide [SP] n region), was assembled into the envelope to generate infective BVs in our recent studies. Here, we identify an additional pathway for Bombyx mori nucleopolyhedrovirus (BmNPV) BV assembly and release that differs, in part, from the currently accepted model for the egress pathway of baculovirus. Electron microscopy showed that during infection, BmNPV-infected cells contained many newly formed multivesicular body (MVB)-like compartments that included mature virions at 30 h postinfection (p.i.). Immunoelectron microscopy demonstrated that the MVBs contained CD63, an MVB endosome marker, and GP64, a BmNPV fusion glycoprotein. MVB fusion with the PM and the release of mature virions, together with naked nucleocapsids, were observed at the cell surface. Furthermore, MVB egress mediated the translocation of SPΔnGP64 to the PM, which induced cell-cell fusion until 36 h p.i. This BV egress pathway can be partially inhibited by U18666A incubation and RNA interference targeting MVB biogenesis genes. Our findings indicate that BmNPV BVs are enveloped and released through MVBs via the cellular exosomal pathway, which is a subordinate BV egress pathway that produces virions with relatively inferior infectivity. This scenario has significant implications for the elucidation of the BmNPV BV envelopment pathway. IMPORTANCE BmNPV is a severe pathogen that infects mainly Bombyx mori, a domesticated insect of economic importance, and accounts for approximately 15% of economic losses in sericulture. BV production plays a key role in systemic BmNPV infection of larvae. Despite the progress made in the functional gene studies of BmNPV, BmNPV BV egress is ill-understood. This study reports a previously unreported MVB envelopment pathway in BmNPV BV egress. To our knowledge, this is the first report of a baculovirus using dual BV egress pathways. This specific BV egress mechanism explains the cause of the non-PM-localized SPΔnGP64-rescued gp64-null bacmid infectivity, elucidating the reason underlying the retention of SP by BmNPV GP64. The data obtained elucidate an alternate molecular mechanism of baculovirus BV egress.

Sesamin Attenuates Obesity-Associated Nonalcoholic Steatohepatitis in High-Fat and High-Fructose Diet-Fed Mice.

This study explored the effects of sesamin on nonalcoholic steatohepatitis (NASH). High-fat and high-fructose diet-fed mice supplemented with or without sesamin. The results suggested that sesamin-treated mice lost body weight and fat tissue weight, had lower levels of serum metabolic parameters, and insulin resistance was mitigated. Histological examinations showed that sesamin treatment mitigated the progression of hepatic steatosis, and inflammation. In addition, sesamin enhanced hepatic antioxidant capacity, and decreased the activations of hepatic c-jun N-terminal kinase, inhibitor of kappa B kinase α, and insulin receptor substrate 1 as well as hepatic interleukin-6 and tumor necrosis factor-alpha levels. Further experiments indicated that sesamin treatment downregulated GRP78 and phospho-inositol-requiring enzyme 1 (IRE1) expression, and upregulated x-box binding protein 1 (XBP1) expression in hepatic tissue. The aforementioned results suggest that sesamin alleviates obesity-associated NASH, which might be linked to the effect of sesamin on the regulation of the hepatic endoplasmic reticulum stress-IRE1/XBP1 pathway. Thus, sesamin may be a good food functional ingredient in the treatment of obesity-associated NASH.

Sesamolin Attenuates Kidney Injury, Intestinal Barrier Dysfunction, and Gut Microbiota Imbalance in High-Fat and High-Fructose Diet-Fed Mice.

This study investigated the effects of sesamolin on kidney injury, intestinal barrier dysfunction, and gut microbiota imbalance in high-fat and high-fructose (HF-HF) diet-fed mice and explored the underlying correlations among them. The results indicated that sesamolin suppressed metabolic disorders and increased renal function parameters. Histological evaluation showed that sesamolin mitigated renal epithelial cell degeneration and brush border damage. Meanwhile, sesamolin inhibited the endotoxin-mediated induction of the Toll-like receptor 4-related IKKα/NF-κB p65 pathway activation. Additionally, sesamolin mitigated intestinal barrier dysfunction and improved the composition of gut microbiota. The correlation results further indicated that changes in the dominant phyla, including Firmicutes, Deferribacterota, Desulfobacterota, and Bacteroidota, were more highly correlated with a reduction in endotoxemia and metabolic disorders, as well as decreases in intestinal proinflammatory response and related renal risk biomarkers. The results of this study suggest that sesamolin attenuates kidney injuries, which might be associated with its effects on the reduction of endotoxemia and related metabolic disorders through the restoration of the intestinal barrier and the modulation of gut microbiota. Thus, sesamolin may be a potential dietary supplement for protection against obesity-associated kidney injury.