Background: Hepatitis E virus (HEV), the leading global cause of acute viral hepatitis, lacks robust in vitro models for virology and pathogenesis research. Objective: We evaluated induced pluripotent stem cell (iPSC)-induced human liver, intestinal and brain organoids (hLOs, hIOs and hBOs) as platforms for HEV infection and replication. Methods: Multilineage organoids were infected with clinical HEV genotypes 1, 3 and 4. Viral tropism, host responses and antiviral efficacy were assessed. Results: All organoids supported the complete life cycle of HEV. hLOs exhibited infection in hepatocytes, cholangiocytes, macrophages and stellate cells, accompanied by elevated interleukin-6 levels, impaired hepatic function (reduced secretion of albumin and Factor IX) and increased levels of alanine aminotransferase and aspartate aminotransferase, indicating hepatocellular injury. hIOs demonstrated broad epithelial (enterocyte, goblet, Paneth and endocrine) and mesenchymal infection, with disrupted barrier function (loss of tight junction proteins), proinflammatory cytokines upregulation and initiation of epithelial–mesenchymal transition. hBOs showed neuronal tropism, infecting glutamatergic, dopaminergic and GABAergic neurons, as well as astrocytes and oligodendrocytes. An increased number of TH ⁺ dopaminergic neurons was observed. Ribavirin treatment in all three models partially reversed this phenotype. Conclusion: This study established iPSC-induced multilineage organoid infection models, confirming HEV’s capacity for pan-tissue infection and revealing potential pathogenic mechanisms in the liver, intestine and nervous system. This platform provides valuable tools for HEV virology research and antiviral drug development, underscoring the unique value of organoid technology in infectious disease research.

Lactoferrin (Ltf), a naturally active glycoprotein, possesses anti-inflammatory, anti-microbial, anti-tumor, and immunomodulatory activities. Many published studies have indicated that Ltf modulates the proliferation of stem cells. However, the role of Ltf in the proliferation of satellite cells, an important cell type in muscle regeneration, has not yet been reported. Here, by using Ltf systemic knockout mice, we illustrate the role of Ltf in skeletal muscle. Results shows that Ltf deficiency impaired proliferation of satellite cells (SCs) and the regenerative capability of skeletal muscle. Mechanistic studies showed that ERK1/2 phosphorylation was significantly downregulated after Ltf deletion in SCs. Simultaneously, the cell cycle-related proteins cyclin D and CDK4 were significantly downregulated. Intervention with exogenous recombinant lactoferrin (R-Ltf) at a concentration of 1000 μg/mL promoted proliferation of SCs. In addition, intraperitoneal injection of Ltf effectively ameliorated the skeletal muscle of mice injured by 1.2% BaCl₂ solution. Our results suggest a protective effect of Ltf in the repair of skeletal muscle damage. Ltf holds promise as a novel therapeutic agent for skeletal muscle injuries.

Brown adipose tissue (BAT) is functionally linked to skeletal muscle because both tissues originate from a common progenitor cell, but the precise mechanism controlling muscle-to-brown-fat communication is insufficiently understood. This report demonstrates that the immunoglobulin superfamily containing leucine-rich repeat (Islr), a marker of mesenchymal stromal/stem cells, is critical for the control of BAT mitochondrial function and whole-body energy homeostasis. The mice loss of Islr in BAT after cardiotoxin injury resulted in improved mitochondrial function, increased energy expenditure, and enhanced thermogenesis. Importantly, it was found that interleukin-6 (IL-6), as a myokine, participates in this process. Mechanistically, Islr interacts with NADH: Ubiquinone Oxidoreductase Core Subunit S2 (Ndufs2) to regulate IL-6 signaling; consequently, Islr functions as a brake that prevents IL-6 from promoting BAT activity. Together, these findings reveal a previously unrecognized mechanism for muscle-BAT cross talk driven by Islr, Ndufs2, and IL-6 to regulate energy homeostasis, which may be used as a potential therapeutic target in obesity.

Dehong virus (DEHV) is an emerging filamentous virus of considerable interest. However, research involving DEHV remains limited, and no suitable models exist to investigate its pathogenicity or transmission. In this study, we developed an in vitro neutralization assay to detect DEHV-neutralizing antibodies, as well as an in vivo bioluminescent imaging mouse model based on a pseudovirus system. Our results confirmed that DEHV utilizes the Niemann–Pick disease, type C1 (NPC1) receptor for cellular entry. Additionally, the neutralization assay demonstrated that DEHV antiserum does not exhibit neutralizing activity against Mengla or Marburg viruses. This pseudovirus-based system provides a valuable platform for studying DEHV biology and evaluating therapeutic interventions. IMPORTANCE: Bats serve as natural reservoirs for diverse filoviruses across Africa, Europe, and East Asia; numerous strains circulate within these populations. Recently, Chinese researchers identified Dehong virus (DEHV), a novel filovirus carried by bats in China. However, the mechanisms underlying the pathogenicity and transmission of DEHV remain poorly understood. Similar to Ebola virus and Marburg virus (MARV), DEHV uses the Niemann–Pick disease, type C1 (NPC1) receptor for host cell invasion. In this study, we utilized a well-established in vitro neutralization assay to confirm that DEHV antiserum lacks neutralizing activity against Mengla and MARV pseudoviruses. Furthermore, we developed an innovative in vivo bioluminescent imaging mouse model using DEHV pseudovirus, which offers a visually intuitive and efficient platform for evaluating antiviral therapies and vaccine candidates. This model has considerable potential for advancing research into DEHV pathogenesis and treatment strategies.

Hepatitis E virus (HEV) is a zoonotic pathogen and the main cause of acute viral hepatitis in China, resulting in a significant burden on public health. Developing a highly efficient in vitro culture system for HEV is crucial for understanding the determinants of HEV infection in humans and other animals, the pathogenic mechanisms, as well as the screening and evaluation of antiviral drugs. In this paper, the research progress on HEV in vitro culture systems is reviewed to provide a convenient reference for further research on HEV, aiding comprehensive efforts toward the widespread prevention and control of related diseases.