As intracellular parasites, viruses depend heavily on host cell structures and their functions to complete their life cycle and produce new viral particles. Viruses utilize or modulate cellular translational machinery to achieve efficient replication; the role of ribosome biogenesis and protein synthesis in viral replication particularly highlights the importance of the ribosome quantity and/or quality in controlling viral protein synthesis. Recently reported studies have demonstrated that ribosome biogenesis factors (RBFs) and ribosomal proteins (RPs) act as multifaceted regulators in selective translation of viral transcripts. Here we summarize the recent literature on RBFs and RPs and their association with subcellular redistribution, post-translational modification, enzyme catalysis, and direct interaction with viral proteins. The advances described in this literature establish a rationale for targeting ribosome production and function in the design of the next generation of antiviral agents.

Background: The highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) emerging in China exhibits high fatality to pigs. However, the mechanism related to the increased pathogenicity of the virus remains unclear. In the present study, the differences in tissue tropism between the highly pathogenic PRRSV strain (JXwn06) and the low pathogenic PRRSV strain (HB-1/3.9) were investigated using PRRSV-specific immunohistochemistry (IHC) staining to provide evidence for elucidating possible mechanism of the pathogenicity of Chinese highly pathogenic PRRSV. Findings: IHC examination showed that PRRSV antigen in the tissues including spleen, tonsil, thymus, kidney, cerebellum, stomach, small intestine, large intestine, turbinal bone and laryngeal cartilage was positive in more pigs inoculated with JXwn06 than HB-1/3.9, and the tissues including trachea, esophagus, liver, mandibular gland and thyroid gland were positive for viral antigen in the pigs inoculated with JXwn06, but not in the pigs inoculated with HB-1/3.9. Meanwhile, we observed that epithelium in tissues including interlobular bile duct in liver, distal renal tubule of kidney, esophageal gland and tracheal gland were positive for viral antigen only in JXwn06-inoculated pigs, and epithelium of gastric mucosa and fundic gland, and intestinal gland were positive for viral antigen in both JXwn06- and HB-1/3.9-inoculated pigs, using monoclonal antibodies to N and Nsp2 proteins. Conclusions: Taken together, these findings indicate that the highly pathogenic PRRSV JXwn06 displays an expanded tissue tropism in vivo, suggesting this may contribute to its high pathogenicity to pigs.

The rapid evolution of pathogen threats and pandemic risks has intensified the demand for adaptable vaccine platforms with rapid design-to-clinical timelines. The success of BNT162b2 and mRNA-1273 in controlling COVID-19 has led to unprecedented changes in vaccine development. Compared with traditional platforms, mRNA vaccines offer distinct advantages: avoiding genomic insertion risks of DNA vaccines; facilitating rapid, scalable production via in vitro transcription; and enabling new modular antigen design against evolving pathogens. However, the development of mRNA vaccines for infectious diseases still faces challenges, including structural stability, translation efficiency, and targeted delivery. This review presents cutting-edge strategies for designing antigens, optimizing mRNA structural elements, and optimizing delivery systems to target infectious pathogens. This study provides a detailed explanation of antigen optimization strategies for different types of mRNA vaccines and explores the potential applications of broad-spectrum and combination mRNA vaccines in human and animal pathogens. Finally, we address the current challenges and future prospects of mRNA vaccine technology, aiming to inform and accelerate the development of next-generation vaccines against emerging pathogens through the integration of these innovations.

Ustiloxins are a group of cyclopeptide mycotoxins produced by rice false smut pathogen Villosiclava virens (anamorph: Ustilaginoidea virens) which seriously threaten the safety production of rice and the health of humans and livestock. Ustiloxin A, accounting for 60% of the total ustiloxins, is the main toxic component. Biotransformation, a process of modifying the functional groups of compounds by means of regio- or stereo-specific reactions catalyzed by the enzymes produced by organisms, has been considered as an efficient way to detoxify mycotoxins. In this study, the endophytic fungus Petriella setifera Nitaf10 was found to be able to detoxify ustiloxin A through biotransformation. Two transformed products were obtained by using the cell-free extract (CFE) containing intracellular enzymes of P. setifera Nitaf10. They were structurally characterized as novel ustiloxin analogs named ustiloxins A1 (1) and A2 (2) by analysis of the 1D and 2D NMR and HRESIMS spectra as well as by comparison with known ustiloxins. The cytotoxic activity of ustiloxins A1 (1) and A2 (2) was much weaker than that of ustiloxin A. The biotransformation of ustiloxin A was found to proceed via oxidative deamination and decarboxylation and was possibly catalyzed by the intracellular amine oxidase and oxidative decarboxylase in the CFE. An appropriate bioconversion was achieved by incubating ustiloxin A with the CFE prepared in 0.5 mol/L phosphate buffer (pH 7.0) for 24 to 48 h. The optimum initial pH values for the bioconversion of ustiloxin A were 7–9. Among eight metal ions (Co²⁺, Cu²⁺, Fe³⁺, Zn²⁺, Ba²⁺, Ca²⁺, Mg²⁺ and Mn²⁺) tested at 5 mmol/L, Cu²⁺, Fe³⁺ and Zn²⁺ totally inhibited the conversion of ustiloxin A. In conclusion, detoxification of ustiloxin A through oxidative deamination and decarboxylation is an efficient strategy.

The p53 pathway is a highly complex signaling network including several key regulators. HAUSP is a critical component of the p53 pathway acting as a deubiquitinase for both p53 and its key repressor Mdm2. Here, we identified a novel HAUSP-interacting protein, HLA-B-associated transcript 3 (Bat3) and found it to be capable of inducing p53 stabilization and activation via a HAUSP-dependent mechanism, resulting in cell growth inhibition. Surprisingly, the deubiquitylating enzymatic activity of HAUSP was not required for this phenomenon. Co-immunoprecipitation showed that p53 coexisted in a complex with Bat3 and HAUSP in vivo, and HAUSP may serve as a binding mediator to enhance the interaction between p53 and Bat3. Further studies revealed that formation of this three-protein complex interfered with the binding of p53 to its proteasome receptor S5a and promoted the accumulation of p53 in nucleus. Notably, Mdm2 protein abundance is also regulated by Bat3 in the presence of HAUSP. Overexpression of Bat3 and HAUSP increases Mdm2 protein levels without influencing the p53–Mdm2 interaction and Mdm2-mediated p53 ubiquitination, indicating that Bat3–HAUSP-mediated protein stabilization is not specific to p53 and different mechanisms may be involved in Bat3-mediated regulation of p53–Mdm2 pathway. Together, our study unravels a novel mechanism by which p53 is stabilized and activated by HAUSP-mediated interaction with Bat3 and implies that Bat3 might function as a tumor suppressor through the stabilization of p53.