A Perspective on Organoids for Virology Research

Abstract

Animal models and cell lines are invaluable for virology research and host–pathogen interaction studies. However, it is increasingly evident that these models are not sufficient to fully understand human viral diseases. With the advent of three-dimensional organotypic cultures, it is now possible to study viral infections in the human context. This perspective explores the potential of these organotypic cultures, also known as organoids, for virology research, antiviral testing, and shaping the virology landscape.

Autophagy-enhancing drugs limit mucosal HIV-1 acquisition and suppress viral replication ex vivo

“…Furthermore, different cell types exhibit specific levels of basal autophagy and thresholds to respond to autophagy triggers, resulting in different magnitudes of autophagy activation, which further contributes to the cell-specific differences in response to drug treatment 26 . Thus, our findings further underscore the importance of analyzing drug effects on multiple primary HIV-1 cellular targets, and on utilizing experimental infection models that more closely reiterate cellular diversity and relevant microenvironments, such as tissue biopsies or human organoid technology, for antiviral drug screening ex vivo 45 .…”

Cell-type-resolved quantitative proteomics map of interferon response against SARS-CoV-2

“…Three-dimensional (3D) organotypic cultures can mimic different organs of interest and allows to study SARS-CoV-2 infection in a more physiological context (Clevers, 2020;Sridhar et al, 2020). However, generating 3D organoids is technically challenging and expensive, and thus cell models are commonly employed as a simple and fast solution to study viral infection.…”

Harness Organoid Models for Virological Studies in Animals: A Cross-Species Perspective

“…In addition, tissue explant cultures—which require rushed handling after surgeries to transiently retain physiologic relevance of cell organization/interaction— undergo cell phenotypic loss and senescence in order to align with an adequate time-window for performing studies in virology and antiviral immunology ( Shanks et al, 2009 ; Mead and Karp, 2019 ; Corrò et al, 2020 ; Schutgens and Clevers, 2020 ; Hofer and Lutolf, 2021 ). Hence, these model systems each exhibit a meaningful gap to recapitulate the cellular organization and physiology of original organs; this is especially true for studying virus-host interactions, which generally involve more than one cell type in the targeted tissues ( Barrila et al, 2018 ; Ramani et al, 2018 ; Bar-Ephraim et al, 2020 ; Sridhar et al, 2020 ; Yuki et al, 2020 ). Upon thorough examination of recent advent and peer reviews in both humans and animals organoid research, it is clear that an urgent need has emerged to harness better biological systems; a balance between practicability and faithfulness is needed to assess the cross-species potential of viral pathogens in both humans and animals ( Shanks et al, 2009 ; Barrila et al, 2018 ; Ramani et al, 2018 ; Montes-Olivas et al, 2019 ; Bar-Ephraim et al, 2020 ; Corrò et al, 2020 ; Sridhar et al, 2020 ; Yuki et al, 2020 ).…”

“…Hence, these model systems each exhibit a meaningful gap to recapitulate the cellular organization and physiology of original organs; this is especially true for studying virus-host interactions, which generally involve more than one cell type in the targeted tissues ( Barrila et al, 2018 ; Ramani et al, 2018 ; Bar-Ephraim et al, 2020 ; Sridhar et al, 2020 ; Yuki et al, 2020 ). Upon thorough examination of recent advent and peer reviews in both humans and animals organoid research, it is clear that an urgent need has emerged to harness better biological systems; a balance between practicability and faithfulness is needed to assess the cross-species potential of viral pathogens in both humans and animals ( Shanks et al, 2009 ; Barrila et al, 2018 ; Ramani et al, 2018 ; Montes-Olivas et al, 2019 ; Bar-Ephraim et al, 2020 ; Corrò et al, 2020 ; Sridhar et al, 2020 ; Yuki et al, 2020 ). The status and perspective of organoid systems has been particularly reviewed, demonstrating potency and comparative advantages in order to fulfill most needs for in vitro modeling of viral infections and pathogenesis in humans ( Barrila et al, 2018 ; Ramani et al, 2018 ; Lehmann et al, 2019 ; Montes-Olivas et al, 2019 ; Bar-Ephraim et al, 2020 ; Kim et al, 2020 ; Sridhar et al, 2020 ; Yuki et al, 2020 ).…”