Abstract
Enteroviruses are important causes of hand, foot, and mouth disease, respiratory infections, and neurological infections in human. A major hurdle for the development of anti-enterovirus agents is the lack of physiologically relevant evaluation platforms that closely correlate with the in vivo state. We established the human small intestinal organoids as a novel platform for characterizing the viral replication kinetics and evaluating candidate antivirals for enteroviruses. The organoids supported productive replication of enterovirus (EV)-A71, coxsackievirus B2, and poliovirus type 3, as evidenced by increasing viral loads, infectious virus titers, and the presence of cytopathic effects. In contrast, EV-D68, which mainly causes respiratory tract infection in humans, did not replicate significantly in the organoids. The differential expression profiles of the receptors for these enteroviruses correlated with their replication kinetics. Using itraconazole as control, we showed that the results of various antiviral assays, including viral load reduction, plaque reduction, and cytopathic effect inhibition assays, were highly reproducible in the organoids. Moreover, itraconazole attenuated virus-induced inflammatory response in the organoids, which helped to explain its antiviral effects and mechanism. Collectively, these data showed that the human small intestinal organoids may serve as a robust platform for investigating the pathogenesis and evaluating antivirals for enteroviruses.
Highlights
Introduction iationsEnteroviruses are small, non-enveloped RNA viruses belonging to the genusEnterovirus in the family Picornaviridae that are associated with major human and mammalian diseases
Our results showed that the human small intestinal organoid model is a physiologically relevant model that supports the productive replication of various enteroviruses and may serve as a reliable platform for evaluating candidate anti-enteroviral agents
To investigate the susceptibility of human small intestinal organoids to infections by human-pathogenic enteroviruses belonging to different species, we infected the organoids with Enterovirus A71 (EV-A71), coxsackievirus B2 (CVB2), poliovirus type 3 (PV-3), and enterovirus D68 (EV-D68) with a multiplicity of infection (MOI) of 0.01
Summary
Enteroviruses are small, non-enveloped RNA viruses belonging to the genus. Enterovirus in the family Picornaviridae that are associated with major human and mammalian diseases. There are 15 species in the genus Enterovirus [1]. Most of the humanpathogenic enteroviruses belong to the species Enterovirus A to D or Rhinovirus A to C. Humans mainly acquire enteroviruses through the fecal-oral route and, sometimes, via the respiratory tract. Enteroviruses replicate in the pharynx and small intestinal submucosal lymphoid tissues and mature polarized enterocytes [2]. Enteroviruses pass to regional lymph nodes and cause transient viremia to infect reticuloendothelial tissues including liver, spleen, and bone marrow. Enterovirus A71 (EV-A71), a major cause of hand, foot, Licensee MDPI, Basel, Switzerland
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
