Enteroviruses (EVs) are highly prevalent viruses world-wide, causing a wide range of diseases in both children and adults. Insight in the global prevalence of EVs is important to define their clinical significance and total disease burden, and assists in making therapeutic decisions. While many studies have been conducted to describe epidemiology of EVs in specific (sub)populations and patient cohorts, little effort has been made to aggregate the available evidence. In the current study, we conducted a search in the PubMed and Embase (Ovid) databases to identify articles reporting EV prevalence and type distribution. We summarized the findings of 153 included studies. We found that EVs are highly prevalent viruses in all continents. Enterovirus B was the most detected species worldwide, while the other species showed continent-specific differences, with Enterovirus C more detected in Africa and Enterovirus A more detected in Asia. Echovirus 30 was by far the most detected type, especially in studies conducted in Europe. EV types in species Enterovirus B—including echovirus 30—were often detected in patient groups with neurological infections and in cerebrospinal fluid, while Enterovirus C types were often found in stool samples.

Non-polio enteroviruses (EV) belonging to species C, which are highly prevalent in Africa, mainly among children, are poorly characterized, and their pathogenesis is mostly unknown as they are difficult to culture. In this study, human airway and intestinal organotypic models were used to investigate tissue and cellular tropism of three EV-C genotypes, EV-C99, CVA-13, and CVA-20. Clinical isolates were obtained within the two passages of culture on Caco2 cells, and all three viruses were replicated in both the human airway and intestinal organotypic cultures. We did not observe differences in viral replication between fetal and adult tissue that could potentially explain the preferential infection of infants by EV-C genotypes. Infection of the airway and the intestinal cultures indicates that they both can serve as entry sites for non-polio EV-C. Ciliated airway cells and enterocytes are the target of infection for all three viruses, as well as enteroendocrine cells for EV-C99.

Halofuginone hydrobromide has shown potent antiviral efficacy against a variety of viruses such as SARS-CoV-2, dengue, or chikungunya virus, and has, therefore, been hypothesized to have broad-spectrum antiviral activity. In this paper, we tested this broad-spectrum antiviral activity of Halofuginone hydrobomide against viruses from different families (Picornaviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, and Flaviviridae). To this end, we used relevant human models of the airway and intestinal epithelium and regionalized neural organoids. Halofuginone hydrobomide showed antiviral activity against SARS-CoV-2 in the airway epithelium with no toxicity at equivalent concentrations used in human clinical trials but not against any of the other tested viruses.

Disease modelling plays a fundamental role in biomedical research, even more in virology where the virus depends strictly on its host for replication. Although animal models are extensively used in virology, there is an increasing demand for animal‐free research. Therefore, during this transition, it is crucial to learn and take advantage of animal research to better implement new emerging models. In this study, we aim to systematically review the translation from animal models to humans for the well‐characterized viral disease polio, as a reference for novel in vitro models in virology. We found a high risk of bias in the included studies and a large diversity of animal models. Moreover, we showed that animal models for studying poliovirus pathogenesis are mainly discrimination models focusing on specific aspects of the disease allowing an insightful understanding of the complex poliovirus infection. Our review underlines the importance of proper standardization of new emerging models and a careful interpretation of the results from discrimination models.

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) causes a major burden of disease. The host response in RSV-LRTI is characterized by airway epithelial injury, inflammation and neutrophil influx, with the formation of neutrophil extracellular traps (NETs). However, the precise role of NETs in the pathophysiology of RSV-LRTI remains to be elucidated. Here, we used well-differentiated human airway epithelial cultures (HAE) of a pediatric and adult donor to study whether NETs cause airway epithelial injury and inflammation in the setting of RSV infection. The exposure of uninfected and RSV-infected HAE cultures to NETs, as produced by stimulation of neutrophils by a low dose of phorbol 12-myristate 13-acetate (PMA), did not induce or aggravate cell injury or inflammation. RSV infection of HAE cultures caused release of pro-inflammatory cytokines such as IL-6 and RANTES in both adult and pediatric cultures, but the differential gene expression for regulated cell death differed between culture donors. In this in vitro airway epithelial model, NETs in the setting of RSV infection did not cause or aggravate epithelial injury or inflammation.

Enteroviruses (EV) usually cause acute, mild, self-limiting disease. Chronic infections with EVs are rare, and typically occur in patients with immunodeficiency, posing a high risk of severe outcomes. We report a rare case of chronic diarrhea caused by coxsackievirus A1 (CVA1) (from EV-C species) infection in a patient with a common variable immunodeficiency, who was on treatment with pooled intravenous immunoglobulin (IVIG) from the Netherlands. To explore treatment options, we assessed the presence of neutralizing antibodies (nAbs) against CVA1 in pooled IVIG from South Africa, where EV-Cs are prevalent, and tested the antiviral efficacy of US Food and Drug Administration–approved drugs like fluoxetine, itraconazole, ribavirin, and remdesivir (RDV) against CVA1 in vitro. Both Dutch and South African IVIG showed low nAb titers against CVA1. The patient, treated with Dutch IVIG, also received a combination of amantadine and fluoxetine, which were discontinued due to side effects. Among the drugs tested, only RDV significantly inhibited CVA1 replication in rhabdomyosarcoma (RD) cells. This in vitro efficacy was not reflected by a favorable clinical response after treatment of the patient with RDV. In concordance with unfavorable antiviral response in the patient, preliminary tests on a co-culture model containing isogenic human intestinal cells and intestinal fibroblasts showed no significant reduction in CVA1 RNA copies after RDV administration. In conclusion, our results showed that repurposing of drugs that have shown in vitro efficacy does not translate well to the patients, and this is also reflected in a more physiologically relevant model of the human intestine.