Development of Three-Dimensional Human Intestinal Organoids as a Physiologically Relevant Model for Characterizing the Viral Replication Kinetics and Antiviral Susceptibility of Enteroviruses

Tsang, Jessica Oi-Ling and Zhou, Jie and Zhao, Xiaoyu and Li, Cun and Zou, Zijiao and Yin, Feifei and Yuan, Shuofeng and Yeung, Man-Lung and Chu, Hin and Chan, Jasper Fuk-Woo (2021) Development of Three-Dimensional Human Intestinal Organoids as a Physiologically Relevant Model for Characterizing the Viral Replication Kinetics and Antiviral Susceptibility of Enteroviruses. Biomedicines, 9 (1). p. 88. ISSN 2227-9059

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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.

Item Type: Article
Uncontrolled Keywords: antiviral; enterovirus; intestinal; organoids; platform
Subjects: STM Repository > Biological Science
Depositing User: Managing Editor
Date Deposited: 03 Oct 2024 04:43
Last Modified: 03 Oct 2024 04:43
URI: http://classical.goforpromo.com/id/eprint/999

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