The role of inflammasome in chronic viral hepatitis.

Infections of hepatotropic viruses cause a wide array of liver diseases including acute hepatitis, chronic hepatitis and the consequently developed cirrhosis and hepatocellular carcinoma (HCC). Among the five classical hepatotropic viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) usually infect human persistently and cause chronic hepatitis, leading to major troubles to humanity. Previous studies have revealed that several types of inflammasomes are involved in the infections of HBV and HCV. Here, we summarize the current knowledge about their roles in hepatitis B and C. NLRP3 inflammasome can be activated and regulated by HBV and HCV. It is found to exert antiviral function or mediates inflammatory response in viral infections depending on different experimental models. Besides NLRP3 inflammasome, IFI16 and AIM2 inflammasomes participate in the pathological process of hepatitis B, and NALP3 inflammasome may sense HCV infection in hepatocytes. The inflammasomes affect the pathological process of viral hepatitis through its downstream secretion of inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 or induction of pyroptosis resulting from cleaved gasdermin D (GSDMD). However, the roles of inflammasomes in different stages of viral infection remains mainly unclear. More proper experimental models of viral hepatitis should be developed for specific studies in future, so that we can understand more about the complexity of inflammasome regulation and multifunction of inflammasomes and their downstream effectors during HBV and HCV infections.

Manganese Dioxide Coated Piezoelectric Nanosonosensitizer for Cancer Therapy with Tumor Microenvironment Remodeling and Multienzyme-Like Catalysis.

Sonodynamic therapy (SDT) as an emerging method for cancer therapy has encountered difficulty in insufficient production of reactive oxygen species (ROS), especially in tumor microenvironment (TME) with elevated antioxidants and hypoxic conditions. In this work, the authors have fabricated heterostructured manganese dioxide (MnO2)-coated BaTiO3 nanoparticles (BTO@M NPs) as a piezoelectric sonosensitizer, which exhibits the capacity of remodeling TME and multienzyme-like catalysis for boosting SDT. Benefitting from the piezotronic effect, the formation of a p-n junction between MnO2 and piezoelectric BTO with a built-in electric field and band bending efficiently promotes the separation of charge carriers, facilitating the generation of superoxide anion (•O2 -) and hydroxyl radical (•OH) under ultrasound (US) stimulation. Moreover, BTO@M NPs can catalyze the overexpressed hydrogen peroxide (H2O2) in TME to produce oxygen for replenishing the gas source in SDT, and also deplete antioxidant glutathione (GSH), realizing TME remodeling. During this process, the reduced Mn(II) can convert H2O2 into •OH, further amplifying cellular oxidative damage. With these combination effects, the versatile BTO@M NPs exhibit prominent cytotoxicity and tumor growth inhibition against 4T1 breast cancer. This work provides a feasible strategy for constructing high-efficiency sonosensitizers for cancer SDT.

In Memory of the Virologist Jianguo Wu, 1957-2022.

It is with deep sorrow that we mourn the passing of the virologist Professor Jianguo Wu [...].

Regulation and functions of the NLRP3 inflammasome in RNA virus infection.

Virus infection is one of the greatest threats to human life and health. In response to viral infection, the host's innate immune system triggers an antiviral immune response mostly mediated by inflammatory processes. Among the many pathways involved, the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome has received wide attention in the context of viral infection. The NLRP3 inflammasome is an intracellular sensor composed of three components, including the innate immune receptor NLRP3, adaptor apoptosis-associated speck-like protein containing CARD (ASC), and the cysteine protease caspase-1. After being assembled, the NLRP3 inflammasome can trigger caspase-1 to induce gasdermin D (GSDMD)-dependent pyroptosis, promoting the maturation and secretion of proinflammatory cytokines such as interleukin-1 (IL-1ß) and interleukin-18 (IL-18). Recent studies have revealed that a variety of viruses activate or inhibit the NLRP3 inflammasome via viral particles, proteins, and nucleic acids. In this review, we present a variety of regulatory mechanisms and functions of the NLRP3 inflammasome upon RNA viral infection and demonstrate multiple therapeutic strategies that target the NLRP3 inflammasome for anti-inflammatory effects in viral infection.

Innate Immunity, Inflammation, and Intervention in HBV Infection.

Hepatitis B virus (HBV) infection is still one of the most dangerous viral illnesses. HBV infects around 257 million individuals worldwide. Hepatitis B in many individuals ultimately develops hepatocellular carcinoma (HCC), which is the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. The innate immunity acts as the first line of defense against HBV infection through activating antiviral genes. Along with the immune responses, pro-inflammatory cytokines are triggered to enhance the antiviral responses, but this may result in acute or chronic liver inflammation, especially when the clearance of virus is unsuccessful. To a degree, the host innate immune and inflammatory responses dominate the HBV infection and liver pathogenesis. Thus, it is crucial to figure out the signaling pathways involved in the activation of antiviral factors and inflammatory cytokines. Here, we review the interplay between HBV and the signal pathways that mediates innate immune responses and inflammation. In addition, we summarize current therapeutic strategies for HBV infection via modulating innate immunity or inflammation. Characterizing the mechanisms that underlie these HBV-host interplays might provide new approaches for the cure of chronic HBV infection.