Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly

Krenn, Veronica; Bosone, Camilla; Burkard, Thomas R; Spanier, Julia; Kalinke, Ulrich; Calistri, Arianna; Salata, Cristiano; Christoff, Raissa R.; Garcez, Patrícia P.; Mirazimi, Alì; Knoblich, Jürgen A.

doi:10.1016/j.stem.2021.03.004

Cited by 104 publications

(93 citation statements)

References 127 publications

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“…ZIKV-infected HBOs have shown that replication of the virus killed neural precursors that led to microcephaly [ 1 , 2 ]. The microcephaly model of ZIKV in HBO further showed thinning of the cortices and impaired cortical expansion, which also lead to HBO size reduction [ 4 ]. Neurosphere and HBO infection with Brazilian and African ZIKV strains showed larger reductions in the proliferative zones, greater disruption of the cortical layers, and an increased number of apoptotic cells with the Brazilian compared to the African ZIKV strain [ 5 ].…”

Section: What Rapid Breakthroughs Occurred Studying Pandemic Viruses?mentioning

confidence: 99%

Breakthroughs in microbiology made possible with organoids

Ramírez-Flores

Knoll

2021

PLoS Pathog

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Section: What Rapid Breakthroughs Occurred Studying Pandemic Viruses?mentioning

confidence: 99%

Breakthroughs in microbiology made possible with organoids

Ramírez-Flores

Knoll

2021

PLoS Pathog

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“…Another study also reported that the Zika virus infection caused cell death in organoids and attenuated organoid growth. Importantly, these phenotypes were not observed in the 2D model but in the 3D model [ 71 ]. hiPSC-derived lung organoids (particularly, alveolar epithelial type II (AT2) cells) have been used as a model of SARS-CoV-2 infection [ 72 , 73 , 74 ].…”

Section: Hpsc-derived Organoidsmentioning

confidence: 99%

Complex Organ Construction from Human Pluripotent Stem Cells for Biological Research and Disease Modeling with New Emerging Techniques

Matsumoto

Yamamoto

Takahashi

2021

IJMS

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Human pluripotent stem cells (hPSCs) are grouped into two cell types; embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs). hESCs have provided multiple powerful platforms to study human biology, including human development and diseases; however, there were difficulties in the establishment of hESCs from human embryo and concerns over its ethical issues. The discovery of hiPSCs has expanded to various applications in no time because hiPSCs had already overcome these problems. Many hPSC-based studies have been performed using two-dimensional monocellular culture methods at the cellular level. However, in many physiological and pathophysiological conditions, intra- and inter-organ interactions play an essential role, which has hampered the establishment of an appropriate study model. Therefore, the application of recently developed technologies, such as three-dimensional organoids, bioengineering, and organ-on-a-chip technology, has great potential for constructing multicellular tissues, generating the functional organs from hPSCs, and recapitulating complex tissue functions for better biological research and disease modeling. Moreover, emerging techniques, such as single-cell transcriptomics, spatial transcriptomics, and artificial intelligence (AI) allowed for a denser and more precise analysis of such heterogeneous and complex tissues. Here, we review the applications of hPSCs to construct complex organs and discuss further prospects of disease modeling and drug discovery based on these PSC-derived organs.

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“…Additionally, such research has shown that these viruses differentially engage the interferon system while organoid defects can be rescued by specific type I interferon treatment. In particular, Krenn et al [122] highlighted the efficacy of IFN-β in ameliorating organoid phenotype infected by ZIKV.…”

Section: Most Recent Findingsmentioning

confidence: 99%

Are the Organoid Models an Invaluable Contribution to ZIKA Virus Research?

2021

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In order to prevent new pathogen outbreaks and avoid possible new global health threats, it is important to study the mechanisms of microbial pathogenesis, screen new antiviral agents and test new vaccines using the best methods. In the last decade, organoids have provided a groundbreaking opportunity for modeling pathogen infections in human brains, including Zika virus (ZIKV) infection. ZIKV is a member of the Flavivirus genus, and it is recognized as an emerging infectious agent and a serious threat to global health. Organoids are 3D complex cellular models that offer an in-scale organ that is physiologically alike to the original one, useful for exploring the mechanisms behind pathogens infection; additionally, organoids integrate data generated in vitro with traditional tools and often support those obtained in vivo with animal model. In this mini-review the value of organoids for ZIKV research is examined and sustained by the most recent literature. Within a 3D viewpoint, tissue engineered models are proposed as future biological systems to help in deciphering pathogenic processes and evaluate preventive and therapeutic strategies against ZIKV. The next steps in this field constitute a challenge that may protect people and future generations from severe brain defects.

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Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly

Cited by 104 publications

References 127 publications

Breakthroughs in microbiology made possible with organoids

Breakthroughs in microbiology made possible with organoids

Complex Organ Construction from Human Pluripotent Stem Cells for Biological Research and Disease Modeling with New Emerging Techniques

Are the Organoid Models an Invaluable Contribution to ZIKA Virus Research?

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