Modeling rotavirus infection and antiviral therapy using primary intestinal organoids - PubMed (original) (raw)

doi: 10.1016/j.antiviral.2015.09.010. Epub 2015 Sep 25.

Marcel Bijvelds 1, Wen Dang 1, Lei Xu 1, Annemiek A van der Eijk 2, Karen Knipping 3, Nesrin Tuysuz 4, Johanna F Dekkers 5, Yijin Wang 1, Jeroen de Jonge 6, Dave Sprengers 1, Luc J W van der Laan 6, Jeffrey M Beekman 5, Derk Ten Berge 4, Herold J Metselaar 1, Hugo de Jonge 1, Marion P G Koopmans 2, Maikel P Peppelenbosch 1, Qiuwei Pan 7

Affiliations

Modeling rotavirus infection and antiviral therapy using primary intestinal organoids

Yuebang Yin et al. Antiviral Res. 2015 Nov.

Abstract

Despite the introduction of oral vaccines, rotavirus still kills over 450,000 children under five years of age annually. The absence of specific treatment prompts research aiming at further understanding of pathogenesis and the development of effective antiviral therapy, which in turn requires advanced experimental models. Given the intrinsic limitations of the classical rotavirus models using immortalized cell lines infected with laboratory-adapted strains in two dimensional cultures, our study aimed to model infection and antiviral therapy of both experimental and patient-derived rotavirus strains using three dimensional cultures of primary intestinal organoids. Intestinal epithelial organoids were successfully cultured from mouse or human gut tissues. These organoids recapitulate essential features of the in vivo tissue architecture, and are susceptible to rotavirus. Human organoids are more permissive to rotavirus infection, displaying an over 10,000-fold increase in genomic RNA following 24h of viral replication. Furthermore, infected organoids are capable of producing infectious rotavirus particles. Treatment of interferon-alpha or ribavirin inhibited viral replication in organoids of both species. Importantly, human organoids efficiently support the infection of patient-derived rotavirus strains and can be potentially harnessed for personalized evaluation of the efficacy of antiviral medications. Therefore, organoids provide a robust model system for studying rotavirus-host interactions and assessing antiviral medications.

Keywords: Interferon; Intestinal organoids; Ribavirin; Rotavirus.

Copyright © 2015 Elsevier B.V. All rights reserved.

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