The new porcine epidemic diarrhea (PED) has caused devastating economic losses to the swine industry worldwide. Despite extensive research on the relationship between autophagy and virus infection, the concrete role of autophagy in porcine epidemic diarrhea virus (PEDV) infection has not been reported. In this study, autophagy was demonstrated to be triggered by the effective replication of PEDV through transmission electron microscopy, confocal microscopy, and Western blot analysis. Moreover, autophagy was confirmed to benefit PEDV replication by using autophagy regulators and RNA interference. Furthermore, autophagy might be associated with the expression of inflammatory cytokines and have a positive feedback loop with the NF-κB signaling pathway during PEDV infection. This work is the first attempt to explore the complex interplay between autophagy and PEDV infection. Our findings might accelerate our understanding of the pathogenesis of PEDV infection and provide new insights into the development of effective therapeutic strategies.

Since 2010, the variant porcine epidemic diarrhea virus (PEDV) has been the etiological agent responsible for the outbreak of porcine epidemic diarrhea (PED) worldwide. In this study, a variant PEDV strain YN1 was isolated, serially propagated on the Vero cells and was characterized for 200 passages. To better elucidate the molecular basis of Vero cell adaptation of variant PEDV strains, we sequenced, compared, and analyzed the full-genome sequences of parental YN1 and passages 15, 30, 60, 90, 144, and 200. The results showed that the variations increased with the viral passage. The nucleotides sequences of non-structural protein (NSP)2, NSP4-7, NSP10, NSP12 and NSP13 genes did not change during the Vero cell adaptation process. After comparison of the variation characteristic of classical, variant virulent/attenuated strains, it was found that attenuation of PEDV virus was associated with 9-26 amino acid (aa) changes in open reading frames (ORF) 1a/b and S protein, early termination in ORF3, 1–3 aa changes in E, M and N protein and some nucleotide sequences’ synonymous mutations. The aa deletion at about 144 aa of S protein could be the attenuation marker for the PEDV. The pig study showed that the early termination in ORF3 was more important for virus cell adaptation than virus attenuation.

Understanding the complex interplay between diarrheic viruses and their hosts is central to combating the global burden of viral gastroenteritis in both humans and animals. The Research Topic "Unraveling Diarrheic Virus–Host Interactions: Mechanisms and Implications" presents seven diverse articles spanning molecular virology, host immune modulation, diagnostic innovation, gut microbiota dysbiosis, and outbreak investigation. Together, these studies provide fresh insights into virus–host dynamics and point toward translational strategies for diagnosis, prevention, and treatment. Viruses and the Gut Ecosystem: From Microbiota to Metabolomics Li et al. reviewed the diverse factors shaping piglet gut microbiota, including host genetics, maternal influences, feeding environment, diet, and pathogenic challenge by porcine epidemic diarrhea virus (PEDV). Their analysis highlighted how PEDV disrupts the intestinal barrier and microbial balance, and discussed the potential of Chinese herbal medicine, particularly Qiwen Huangbai San, to restore mucosal immunity and promote microbial homeostasis. To investigate the gut microbiota's role in human viral gastroenteritis, Wang et al. performed a metagenomic study in children with norovirus infection. They found persistent dysbiosis, enrichment of Bacteroides uniformis and Veillonella, and altered carbohydrate and lipid metabolic pathways that correlated with disease severity, offering candidate biomarkers for diagnosis and therapy. Host-Targeted Antivirals and Mechanistic Insights The antiviral potential of Saxifraga stolonifera was explored by Zhou et al., who demonstrated that this plant disrupts the PEDV nucleocapsid protein's interaction with host p53. They identified quercetin and other bioactive components as key effectors and, through network pharmacology and molecular docking, linked these compounds to modulation of p53-related signaling pathways, highlighting a host-targeted antiviral approach. Zhang et al. reported that mutation of the K48 ubiquitin linkage site in host cells markedly reduced murine norovirus replication. This was achieved by creating a non-permissive, pro-inflammatory environment, revealing the importance of ubiquitination dynamics in viral propagation. Surveillance, Epidemiology, and Diagnostic Innovation Long-term epidemiological monitoring of norovirus in Shenzhen was carried out by Chen et al., who analyzed seven years of surveillance data. Their study uncovered genotype shifts, recombination breakpoints, and mutations associated with viral evolution, with infections concentrated in children under three years old and peaking during winter in more developed districts. In an outbreak investigation, Liu et al. identified airborne transmission from vomitus exposure as the main route of spread for sapovirus in a Shenzhen school. They showed that prompt decontamination and adherence to standard vomit cleanup protocols significantly reduced case numbers. Xu et al. developed a multiplex TaqMan MGB qPCR assay for simultaneous detection of four major feline viruses. The assay demonstrated high sensitivity, specificity, and throughput, enabling rapid diagnostics in multi-pathogen infection scenarios, which are increasingly common in clinical veterinary practice. Perspectives and Future Directions Collectively, these articles underscore the complexity and translational potential of research into diarrheic virus–host interactions. Several unifying themes emerge: Microbiota–immune crosstalk is both a driver and consequence of viral infections. Host-directed antivirals, whether herbal-derived or targeting ubiquitin pathways, hold promise for reducing resistance development. Integrated surveillance and innovative diagnostics remain central to early detection and containment, especially in high-density or zoonotic contexts. Looking ahead, integrating systems biology, multi-omics, structural virology, and interactomics will be crucial for identifying universal host targets and novel therapeutics. Bridging laboratory discoveries with field-ready applications will accelerate progress in controlling viral gastroenteritis across species.