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Rosavirus is a newly discovered member of the family Picornaviridae that was initially detected in wild rodents and subsequently in children with diarrhoea. Nevertheless, there is a significant gap in our understanding of the geographical distribution, phylogenetic relationships, evolutionary patterns, and transmission of rosaviruses. To address these issues, we analysed 434 rodents and shrews from five different species that were collected in southern China. Using PCR screening of faecal samples, we detected rosaviruses in Norway rats ( Rattus norvegicus ) and identified two previously undocumented host species: tanezumi rats ( Rattus tanezumi ) and Asian house shrews ( Suncus murinus ). Rosaviruses were particularly common in these animals, with an overall prevalence rate of 32.49% (141/434). For genetic and evolutionary analyses, we selected six representative positive samples to amplify the complete genomes of rosaviruses. Bayesian phylogenetic analysis suggested that our sequences clustered within the genus Rosavirus, where genotype B sequences are the closest relatives. The elevated nonsynonymous-to-synonymous ratios observed in rosavirus B may be attributed to relaxed selection pressures driven by virus spillover events. On the basis of the available data, it is hypothesized that the genus Rosavirus may have originated from Norway rats around the year 1339. In summary, these findings provide valuable insights into the complex evolutionary history of rosaviruses and underscore the urgent need for ongoing surveillance of this virus.

Seneca Valley virus (SVV), a new member of Picornaviridae , causes idiopathic vesicular symptoms in pregnant sows and acute death in neonatal piglets, considerably damaging the swine industry. The viral protease 3C (3C pro ) cleaves host immune-related molecules to create a favorable environment for viral replication. In this study, we found that mRNA decapping enzyme 1A (DCP1A) is a novel antiviral effector against SVV infection that targets 3D viral RNA-dependent RNA polymerase for OPTN-mediated autophagic degradation. To counteract this effect, SVV 3C pro targets DCP1A for cleavage at glutamine 343 (Q343), resulting in the cleaved products DCP1A (1–343) and DCP1A (344–580), which lose the ability to restrict SVV replication. In contrast, the 3C cleavage-resistant DCP1A-Q343A mutant exhibited stronger antiviral effects than the wild-type DCP1A. Additionally, the degradation of the viral 3D protein targeted by DCP1A was abolished after its cleavage by SVV 3C pro . In conclusion, our study demonstrated that SVV 3C pro is a pivotal ISG antagonist that cleaves DCP1A. These results offer novel insight into how viruses evade host immunity.

Seneca Valley virus (SVV) is known to cause vesicular disease in swine, presenting new challenges to the pig industry. Recent studies have investigated the relationship between disrupted copper ion homeostasis and viral replication, suggesting that copper dysregulation has a significant impact on the replication of various viruses. Research has also shown that mitochondria-associated endoplasmic reticulum membrane (MAM) and NF-κB are involved in the innate immune response triggered by viral infections. However, the exact mechanisms by which copper (Cu), MAM, and NF-κB affect SVV replication remain unclear. In this study, it was found that SVV induces an imbalance in copper homeostasis, leading to dynamic changes in MAM while inhibiting the NF-κB pathway. This inhibition results in decreased levels of IL-6, IL-1β, TNF-α, IFN-α, and IFNλ3. Furthermore, the disruption of copper homeostasis in SVV-infected PK-15 cells regulates the NF-κB pathway through MAM, promoting SVV replication. This research provides valuable insights into the regulation of copper metabolism during SVV infection and establishes a theoretical framework for understanding the pathogenesis and immune activation mechanisms associated with SVV.

The phospholipase PLA2G16 is required for the entry of picornaviruses, and in its absence, virus infection is prevented by a galectin-8-mediated process. The role of PLA2G16 in picornavirus replication Thijn Brummelkamp and colleagues use a genome-wide haploid genetic screen to identify the host factors required for the replication of picornaviruses. They identify the small phospholipase PLA2G16 as being required for the cytoplasmic delivery of the viral genome. In a second screen to find mutants that restored virus susceptibility to PLA2G16-deficient cells, the authors identify galectin-8, a sensor previously implicated in the autophagic clearance of intracellular bacteria. The precise function of PLA2G16 remains unclear, but the authors suggest that it facilitates the displacement of the viral genome from galactin-8-positive vesicles. Picornaviruses are a leading cause of human and veterinary infections that result in various diseases, including polio and the common cold. As archetypical non-enveloped viruses, their biology has been extensively studied 1 . Although a range of different cell-surface receptors are bound by different picornaviruses 2 , 3 , 4 , 5 , 6 , 7 , it is unclear whether common host factors are needed for them to reach the cytoplasm. Using genome-wide haploid genetic screens, here we identify the lipid-modifying enzyme PLA2G16 (refs 8 , 9 , 10 , 11 ) as a picornavirus host factor that is required for a previously unknown event in the viral life cycle. We find that PLA2G16 functions early during infection, enabling virion-mediated genome delivery into the cytoplasm, but not in any virion-assigned step, such as cell binding, endosomal trafficking or pore formation. To resolve this paradox, we screened for suppressors of the Δ PLA2G16 phenotype and identified a mechanism previously implicated in the clearance of intracellular bacteria 12 . The sensor of this mechanism, galectin-8 (encoded by LGALS8 ), detects permeated endosomes and marks them for autophagic degradation, whereas PLA2G16 facilitates viral genome translocation and prevents clearance. This study uncovers two competing processes triggered by virus entry: activation of a pore-activated clearance pathway and recruitment of a phospholipase to enable genome release.

Senecavirus A (SVA) is an emerging pathogen that causes idiopathic vesicular infections in pig herds, posing a potential threat to their production performance. Heat shock protein 70 (Hsp70) is a molecular chaperone that plays an important role in host homeostasis under both physiological and stress conditions. However, the effects of Hsp70 on SVA infection and its underlying regulatory mechanisms remain unclear. Here, we confirmed that Hsp70 expression promotes SVA infection, as evidenced by the expression of viral proteins, viral titers, and the number of rSVA-eGFP-infected cells. This positive regulatory role of Hsp70 is mainly involved in post-entry stages of SVA. Viral proteins that interacted with Hsp70 were screened, and co-immunoprecipitation (co-IP) shows an interaction between Hsp70 and SVA L and 3D proteins. Subsequently, we determined that the expression of Hsp70 is beneficial for the stability of the SVA L and 3D proteins. Additionally, the substrate-binding domain (SBD) of Hsp70 plays an important role in the interaction between Hsp70 and SVA L or 3D proteins; and the deletion of this domain results in the loss of the stabilizing effect of Hsp70 on SVA L and 3D proteins and the positive regulatory effect of Hsp70 on SVA replication. These results reveal that Hsp70 promotes SVA infection by stabilizing viral L and 3D proteins and provides a strategy for preventing and controlling SVA infection.

Infected cells can undergo apoptosis as a protective response to viral infection, thereby limiting viral infection. As viruses require a viable cell for replication, the death of the cell limits cellular functions that are required for virus replication and propagation. Picornaviruses are single-stranded RNA viruses that modify the host cell apoptotic response, probably in order to promote viral replication, largely as a function of the viral proteases 2A, 3C, and 3CD. These proteases are essential for viral polyprotein processing and also cleave cellular proteins. Picornavirus proteases cleave proapoptotic adaptor proteins, resulting in downregulation of apoptosis. Picornavirus proteases also cleave nucleoporins, disrupting the orchestrated manner in which signaling pathways use active nucleocytoplasmic trafficking, including those involved in apoptosis. In addition to viral proteases, the transmembrane 2B protein alters intracellular ion signaling, which may also modulate apoptosis. Overall, picornaviruses, via the action of virally encoded proteins, exercise intricate control over and subvert cell death pathways, specifically apoptosis, thereby allowing viral replication to continue.

The intricate connection between the gut and the brain involves multiple routes. Several viral families begin their infection cycle in the intestinal tract. However, amongst the long list of viral intestinal pathogens, picornaviruses, and astroviruses stand out for their ability to transition from the intestinal epithelia to central or peripheral nervous system cells. In immunocompromised, neonates and young children, these viral infections can manifest as severe diseases, such as encephalitis, meningitis, and acute flaccid paralysis. What confers this remarkable plasticity and makes them efficient in infecting cells of the gut and the brain axes? Here, we review the current understanding of the virus infection along the gut-brain axis for some enteric viruses and discuss the molecular mechanisms of their attenuation.

Seneca Valley virus (SVV) infection leads to severe vesicular diseases in pigs, posing a significant threat to the global swine industry. Ferroptosis, a novel form of non-apoptotic cell death, is characterized by iron-dependent phospholipid peroxidation. However, the role of ferroptosis in SVV replication remains poorly understood. In this study, we demonstrate that SVV infection induces ferroptosis, as evidenced by lipid peroxidation, reactive oxygen species (ROS) accumulation, and glutathione (GSH) depletion. The GPX4 and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy are key contributors to ferroptosis induction. Furthermore, our findings reveal that the SVV 3 C proteinase (3C pro ) targets the GPX4 for degradation, thereby promoting ferroptosis. Simultaneously, the SVV 3D protein enhances the NCOA4-FTH1 interaction, leading to increased ferritin degradation and subsequent ferritinophagy. Notably, inhibition of ferroptosis significantly reduces SVV replication and its associated inflammatory effects. Collectively, these results elucidate the intricate molecular mechanisms underlying SVV-induced ferroptosis, highlighting the synergistic roles of 3C pro and 3D in activating ferroptotic pathways and presenting potential targets for therapeutic intervention in SVV infections.

It remains largely mysterious how the genomes of non-enveloped eukaryotic viruses are transferred across a membrane into the host cell. Picornaviruses are simple models for such viruses, and initiate this uncoating process through particle expansion, which reveals channels through which internal capsid proteins and the viral genome presumably exit the particle, although this has not been clearly seen until now. Here we present the atomic structure of an uncoating intermediate for the major human picornavirus pathogen CAV16, which reveals VP1 partly extruded from the capsid, poised to embed in the host membrane. Together with previous low-resolution results, we are able to propose a detailed hypothesis for the ordered egress of the internal proteins, using two distinct sets of channels through the capsid, and suggest a structural link to the condensed RNA within the particle, which may be involved in triggering RNA release. The detailed mechanism of how non-enveloped viruses initiate infection remains obscure. Ren et al . present the atomic structure of an uncoating intermediate for the human picornavirus CAV16, revealing a major capsid protein partly extruded from the capsid and suggesting a model for RNA release.

Porcine sapelovirus (PSV) is an important emerging pathogen associated with a wide variety of diseases in swine, including acute diarrhoea, respiratory distress, skin lesions, severe neurological disorders, and reproductive failure. Although PSV is widespread, serological assays for field-based epidemiological studies are not yet available. Here, four PSV strains were recovered from diarrheic piglets, and electron microscopy revealed virus particles with a diameter of ~32 nm. Analysis of the entire genome sequence revealed that the genomes of PSV isolates ranged 7569–7572 nucleotides in length. Phylogenetic analysis showed that the isolated viruses were classified together with strains from China. Additionally, monoclonal antibodies for the recombinant PSV-VP1 protein were developed to specifically detect PSV infection in cells, and we demonstrated that isolated PSVs could only replicate in cells of porcine origin. Using recombinant PSV-VP1 protein as the coating antigen, we developed an indirect ELISA for the first time for the detection of PSV antibodies in serum. A total of 516 swine serum samples were tested, and PSV positive rate was 79.3%. The virus isolates, monoclonal antibodies and indirect ELISA developed would be useful for further understanding the pathophysiology of PSV, developing new diagnostic assays, and investigating the epidemiology of the PSV.