No abstract

The accessory proteins of coronaviruses are essential for virus–host interactions and the modulation of host immune responses. It has been reported that accessory protein ORF3a encoded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce apoptosis, and accessory protein ORF6 and ORF8 could be inhibitors of the type-I interferon (IFN) signaling pathway. However, the function of accessory protein ORF7b is largely unknown. We investigated the apoptosis-inducing activity of ORF7b in cells. Cytokine levels and host innate immune responses, including expression of interferon regulatory transcription factor (IRF)-3, signal transducer and activator of transcription (STAT)-1, interferon (IFN)-β, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, were also investigated. We found that ORF7b promoted expression of IFN-β, TNF-α, and IL-6, activated type-I IFN signaling through IRF3 phosphorylation, and activated TNFα-induced apoptosis in HEK293T cells and Vero E6 cells. These results could provide deeper understanding about the pathogenicity of SARS-CoV-2 as well as the interaction between the accessory protein ORF7b with host immune responses.

No abstract

The gut–microbiota–brain axis is the most important complex and bidirectional pathway between the gastrointestinal tract and the central nervous system. This study investigated the potential of microbe‐induced gut‐to‐brain signaling to modulate the effect of stress on depressive‐like behavior, intestinal barrier, and neuroinflammation. Result showed that fecal microbiota transplantation increased the consumption of sucrose solutions and decreased the immobility time in forced swimming test. This treatment also increased Firmicutes and decreased Bacteroidetes and Desulfobacterota at phylum levels; reduced the loss of villi and epithelial cells; suppressed the inflammatory cell infiltration in the ileum; increased the expression of ZO‐1, occludin; protected the mucosal layer function; and suppressed the high levels of inflammasomes (NLRP3, ASC, caspase‐1, and IL‐1β) in rat brain. In summary, fecal microbiota transplantation improves the depressive‐like behavior, alters the gut microbiota imbalance, and alleviates the intestinal tract inflammation, intestinal mucosa disruption, and neuroinflammation in rats induced by chronic unpredictable mild stress.

Viruses struggle to reproduce after infecting cells, and the host eliminates infected cells through apoptosis to prevent virus spread. Cells adopt a special ubiquitination code to protect against viral infection, while ORF7a manipulates and exploits the ubiquitin system to eliminate host cells' effect on apoptosis and redirect cellular pathways in favor of virus survival.