J Bacteriol Virol.  2020 Sep;50(3):168-174. 10.4167/jbv.2020.50.3.168.

Organoids as a New In Vitro Model of Human Norovirus Infection

• Kim JH
• Jeong YI

• KMID: 2512135
• DOI: http://doi.org/10.4167/jbv.2020.50.3.168

Abstract

Human noroviruses (HuNoVs) are the main causative viral agents in epidemic and endemic acute gastroenteritis worldwide. Despite their impact on the global economic and health burden, developing effective control measures to prevent and treat norovirus gastroenteritis remains a difficult problem to solve. One of the major reasons for this problem is the lack of affordable small animal models and a robust and reproducible In Vitro cell culture system for the propagation of this poorly characterized RNA virus. Recently, the development of a 3-dimensional culture system using pluripotent stem cells to mimic the native small intestine has led to the discovery of new strategies for the cultivation of this virus. In this review, we describe a human stem cell-derived intestinal organoid model that led to the development of the currently available HuNoV In Vitroculture systems that support replication of the virus, and provide helpful insights into HuNoV biology and vaccine and therapeutic development.

Keyword

Human noroviruses; Human intestinal enteroids; Human intestinal organoids

Figure

• 

  Fig. 1 Comparison between the culture process and features of HIOs and HIEs.

Reference

1. Graves NS. Acute gastroenteritis. Prim care 2013;40:727-41.DOI: 10.1016/j.pop.2013.05.006. PMID: 23958366. PMCID: PMC7119329.

2. Ahmed SM, Hall AJ, Robinson AE, Verhoef L, Premkumar P, Parashar UD, et al. Global prevalence of norovirus in cases of gastroenteritis: a systematic review and meta-analysis. Lancet Infect Dis 2014;14:725-30.DOI: 10.1016/S1473-3099(14)70767-4.

3. Thorne LG, Goodfellow IG. Norovirus gene expression and replication. J Gge Virol 2014;95:278-91.DOI: 10.1099/vir.0.059634-0. PMID: 24243731.

4. Todd KV, Tripp RA. Human Norovirus: Experimental Models of Infection. Viruses 2019;11:151.DOI: 10.3390/v11020151. PMID: 30759780. PMCID: PMC6410082.

5. Vinjé J. Advances in laboratory methods for detection and typing of norovirus. J Clin Microbiol 2015;53:373-81.DOI: 10.1128/JCM.01535-14. PMID: 24989606. PMCID: PMC4298492.

6. Devasia T, Lopman B, Leon J, Handel A. Association of host, agent and environment characteristics and the duration of incubation and symptomatic periods of norovirus gastroenteritis. EpidemiolInfect 2015;143:2308-14.DOI: 10.1017/S0950268814003288. PMID: 25483148.

7. Shah MP, Hall AJ. Norovirus Illnesses in Children and Adolescents. Infect Dis Clin North Am 2018;32:103-18.DOI: 10.1016/j.idc.2017.11.004. PMID: 29406972. PMCID: PMC6814392.

8. Duizer E, Schwab KJ, Neill FH, Atmar RL, Koopmans MPG, Estes MK. Laboratory efforts to cultivate noroviruses. J Gen Virol 2004;85:79-87.DOI: 10.1099/vir.0.19478-0. PMID: 14718622.

9. Straub TM, Höner zu Bentrup K, Orosz-Coghlan P, Dohnalkova A, Mayer BK, Bartholomew RA, et al. In vitro cell culture infectivity assay for human noroviruses. Emerg Infect Dis 2007;13:396-403.DOI: 10.3201/eid1303.060549. PMID: 17552092. PMCID: PMC2725917.

10. Herbst-Kralovetz MM, Radtke AL, Lay MK, Hjelm BE, Bolick AN, Sarker SS, et al. Lack of norovirus replication and histo-blood group antigen expression in 3-dimensional intestinal epithelial cells. Emerg Infect Dis 2013;19:431-8.DOI: 10.3201/eid1903.121029. PMID: 23622517. PMCID: PMC3647661.

11. Papafragkou E, Hewitt J, Park GW, Greening G, Vinjé J. Challenges of culturing human norovirus in three-dimensional organoid intestinal cell culture models. PloS one 2013;8:e63485.DOI: 10.1371/journal.pone.0063485. PMID: 23755105. PMCID: PMC3670855.

12. Takanashi S, Saif LJ, Hughes JH, Meulia T, Jung K, Scheuer KA, et al. Failure of propagation of human norovirus in intestinal epithelial cells with microvilli grown in three-dimensional cultures. Arch Virol 2014;159:257-66.DOI: 10.1007/s00705-013-1806-4. PMID: 23974469. PMCID: PMC3946686.

13. Zhang YG, Wu S, Xia Y, Sun J. Salmonella-infected crypt-derived intestinal organoid culture system for host-bacterial interactions. Physiol Rep 2014;2:e12147.DOI: 10.14814/phy2.12147. PMID: 25214524. PMCID: PMC4270227.

14. Yin X, Mead BE, Safaee H, Langer R, Karp JM, Levy O. Engineering Stem Cell Organoids. Cell Stem Cell 2016;18:25-38.DOI: 10.1016/j.stem.2015.12.005. PMID: 26748754. PMCID: PMC4728053.

15. Foulke-Abel J, In J, Kovbasnjuk O, Zachos NC, Ettayebi K, Blutt SE, et al. Human enteroids as an ex-vivo model of host-pathogen interactions in the gastrointestinal tract. Exp Biol Med 2014;239:1124-34.DOI: 10.1177/1535370214529398. PMID: 24719375. PMCID: PMC4380516.

16. Leushacke M, Barker N. Ex vivo culture of the intestinal epithelium: strategies and applications. Gut 2014;63:1345-54.DOI: 10.1136/gutjnl-2014-307204. PMID: 24841573.

17. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009;459:262-5.DOI: 10.1038/nature07935. PMID: 19329995.

18. Finkbeiner SR, Zeng XL, Utama B, Atmar RL, Shroyer NF, Estes MK. Stem cell-derived human intestinal organoids as an infection model for rotaviruses. mBio 2012;3:e00159-12.DOI: 10.1128/mBio.00159-12. PMID: 22761392. PMCID: PMC3398537.

19. Zhang D, Tan M, Zhong W, Xia M, Huang P, Jiang X. Human intestinal organoids express histo-blood group antigens, bind norovirus VLPs, and support limited norovirus replication. Sci Rep 2017;7:12621.DOI: 10.1038/s41598-017-12736-2. PMID: 28974702. PMCID: PMC5626734.

20. Etzold S, Bode L. Glycan-dependent viral infection in infants and the role of human milk oligosaccharides. Curr Opin Virol 2014;7:101-7.DOI: 10.1016/j.coviro.2014.06.005. PMID: 25047751.

21. Sato S, Hisaie K, Kurokawa S, Suzuki A, Sakon N, Uchida Y, et al. Human Norovirus Propagation in Human Induced Pluripotent Stem Cell-Derived Intestinal Epithelial Cells. Cell Mol Gastroenterol Hepatol 2019;7:686-8 e5.DOI: 10.1016/j.jcmgh.2018.11.001. PMID: 30543870. PMCID: PMC6477164.

22. Ettayebi K, Crawford SE, Murakami K, Broughman JR, Karandikar U, Tenge VR, et al. Replication of human noroviruses in stem cell-derived human enteroids. Science 2016;353:1387-93.DOI: 10.1126/science.aaf5211. PMID: 27562956. PMCID: PMC5305121.

23. Saxena K, Blutt SE, Ettayebi K, Zeng XL, Broughman JR, Crawford SE, et al. Human Intestinal Enteroids: a New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology. J Virol 2015;90:43-56.DOI: 10.1128/JVI.01930-15. PMID: 26446608. PMCID: PMC4702582.

24. Chang-Graham AL, Danhof HA, Engevik MA, Tomaro-Duchesneau C, Karandikar UC, Estes MK, et al. Human Intestinal Enteroids With Inducible Neurogenin-3 Expression as a Novel Model of Gut Hormone Secretion. Cell Mol Gastroenterol Hepatol 2019;8:209-29.DOI: 10.1016/j.jcmgh.2019.04.010. PMID: 31029854. PMCID: PMC6664234.

25. Kilic T, Koromyslova A, Hansman GS. Structural Basis for Human Norovirus Capsid Binding to Bile Acids. J Virol 2019;93:e01581-18.DOI: 10.1128/JVI.01581-18. PMID: 30355683. PMCID: PMC6321941.

26. Ruvoën-Clouet N, Belliot G, Pendu JL. Noroviruses and histo-blood groups: the impact of common host genetic polymorphisms on virus transmission and evolution. Rev Med Virol 2013;23:355-66.DOI: 10.1002/rmv.1757. PMID: 23959967.

27. Costantini V, Morantz EK, Browne H, Ettayebi K, Zeng XL, Atmar RL, et al. Human Norovirus Replication in Human Intestinal Enteroids as Model to Evaluate Virus Inactivation. Emerg Infect Dis 2018;24:1453-64.DOI: 10.3201/eid2408.180126. PMID: 30014841. PMCID: PMC6056096.