Modeling Human Viral Diseases: Trials and Triumphs

Ayyavoo, Velpandi

doi:10.3389/fviro.2021.722297

Cited by 4 publications

(2 citation statements)

References 37 publications

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“…Historically, studies focused on the pathogenesis of enteric viruses relied on transformed cell lines that lack both the cellular diversity and coordinated function of the gastrointestinal epithelium ( 4 ). Although animal models provide a functional readout and a more holistic model of infection, they are costly, low throughput, and often not susceptible to, or exhibit different symptoms in response to, human enteric virus infection ( 5 ). Within the past decade, virologists have increasingly turned to human intestinal organoids (HIOs) as a tool to further elucidate viral-host interactions.…”

Section: Introductionmentioning

confidence: 99%

Gastrointestinal organoids in the study of viral infections

Gebert

Scribano

Engevik

et al. 2023

American Journal of Physiology-Gastrointestinal and Liver Physi

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Viruses are among the most prevalent enteric pathogens. While virologists historically relied on cell lines and animal models, human intestinal organoids (HIOs) continue to grow in popularity. HIOs are non-transformed, stem cell derived, ex vivo cell cultures that maintain the cell type diversity of the intestinal epithelium. They offer higher throughput than standard animal models while more accurately mimicking the native tissue of infection than transformed cell lines. Here, we review recent literature that highlights virological advances facilitated by HIOs. We discuss the variations and limitations of HIOs, but also how HIOs have allowed for the cultivation of previously uncultivatable viruses and how they have offered insight into tropism, entry, replication kinetics, and host-pathogen interactions. In each case, we discuss exemplary viruses and archetypal studies. We discuss how the speed and flexibility of HIO-based studies contributed to our knowledge of SARS-CoV-2 and anti-viral therapeutics. Finally, we discuss current limitations of HIOs and future directions to overcome these.

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Section: Introductionmentioning

confidence: 99%

Gastrointestinal organoids in the study of viral infections

Gebert

Scribano

Engevik

et al. 2023

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Although immortalized cell lines and an animal model have been used to study PeV-A neuropathology 23 , they come with several limitations. Models based on cell lines lack complexity and biological relevance 24 , while animal models are often not susceptible to human viruses and do not recapitulate the human neurodevelopment 25,26 . Organoids address these shortcomings by not only closely recapitulating the cellular composition, structure, and complexity of the organ they mimic, but also the human neurodevelopment 24 .…”

Section: Introductionmentioning

confidence: 99%

Parechovirus infections in human brain organoids: host immune response and not neuro-infectivity as a correlate of neuropathology

Capendale

García-Rodríguez

Mulder

et al. 2023

Preprint

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Parechovirus A (PeV-A) is a species in the Picornaviridae family that can cause a variety of diseases, mainly in children.The most prevalent genotype, PeV-A1, can causes mild respiratory and gastrointestinal symptoms while the second most prevalent genotype, PeV-A3 can elicit severe neurological disease such as meningoencephalitis in infants. The factors determining differential outcomes between genotypes are poorly understood. In this study, we investigated the viral dynamics and tropism of PeV-A1 and PeV-A3 infection in human induced pluripotent stem cell (hiPSC)-derived unguided neural organoids (UNOs). UNOs supported PeV-A1 and PeV-A3 replication, as measured by RT-qPCR and confirmed by TCID50. Both genotypes showed similar cell tropism and infected neurons and astrocytes. Despite replicating up to a higher titre as compared to PeV-A3, PeV-A1 infection showed no significant cytokine upregulation while PeV-A3 infection resulted in an increased production of IFN-λ1 and CXCL10. This effect was also seen for Echovirus 11, another picornaviruses resulting in neurological disease. Blocking the IFN-pathway with Ruxolitinib resulted in enhanced replication of PeV-A3 indicating IFN-mediated restriction of PeV-A3 replication. This genotype-specific immune response could explain the exacerbated PeV-A3 associated severe clinical neuropathology.

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Advances in porcine respiratory and intestinal organoids: status and potential application for virus infections

Liu,

Dong,

Liu

et al. 2024

One Health Adv.

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The respiratory tract and digestive tract serve as the gateway between the host and the environment, playing an important role in protecting against viral infections. Diseases caused by viruses that infiltrate the respiratory and gastrointestinal tracts account for the major infectious diseases in pigs, resulting in significant economic losses for the swine industry. However, studies on virus-host interactions are limited due to the lack of suitable research models that can effectively stimulate the highly complex physiological characteristics found in vivo. With the advancement in stem cell technology, organoids that more closely recapitulate the structure, function, and organization of specific organs or tissues in vitro have gradually become a research hotspot. These novel ex vivo models are critical for studying viral infection, investigating viral pathogenesis, elucidating virus-host interactions and developing preventive and therapeutic approaches. Currently, respiratory organoids and intestinal organoids (IOs) have been widely applied in the study of infectious diseases. Therefore, this review primarily summarizes the development of porcine respiratory and intestinal organoids, their applications in studying infection, current limitations, and future perspectives.

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Modeling Human Viral Diseases: Trials and Triumphs

Cited by 4 publications

References 37 publications

Gastrointestinal organoids in the study of viral infections

Gastrointestinal organoids in the study of viral infections

Parechovirus infections in human brain organoids: host immune response and not neuro-infectivity as a correlate of neuropathology

Advances in porcine respiratory and intestinal organoids: status and potential application for virus infections

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