Culture and differentiation of rabbit intestinal organoids and organoid-derived cell monolayers

Kardia, Egi; Frese, Michael; Smertina, Elena; Strive, Tanja; Zeng, Xi‐Lei; Estes, Mary K.; Hall, Robyn N.

doi:10.1038/s41598-021-84774-w

Cited by 19 publications

(26 citation statements)

References 57 publications

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“…Until now, research into the non-structural proteins of caliciviruses has mostly been focused on MNV and FCV (mainly because these viruses can be cultivated easily in a laboratory). New organoid culture systems, e.g., human (Ettayebi et al, 2016) and rabbit intestinal organoids (Mussard et al, 2020;Kardia et al, 2021) may soon facilitate detailed functional studies on the replication of human noroviruses, lagoviruses, and other caliciviruses that do not grow in conventional cell culture. These studies will also shed light on the role of non-structural proteins in building replication complexes, counteracting innate and adaptive immune responses, redirecting cellular resources, and other activities.…”

Section: Discussionmentioning

confidence: 99%

Calicivirus Non-structural Proteins: Potential Functions in Replication and Host Cell Manipulation

et al. 2021

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The Caliciviridae are a family of viruses with a single-stranded, non-segmented RNA genome of positive polarity. The ongoing discovery of caliciviruses has increased the number of genera in this family to 11 (Norovirus, Nebovirus, Sapovirus, Lagovirus, Vesivirus, Nacovirus, Bavovirus, Recovirus, Salovirus, Minovirus, and Valovirus). Caliciviruses infect a wide range of hosts that include fishes, amphibians, reptiles, birds, and marine and land mammals. All caliciviruses have a genome that encodes a major and a minor capsid protein, a genome-linked viral protein, and several non-structural proteins. Of these non-structural proteins, only the helicase, protease, and RNA-dependent RNA polymerase share clear sequence and structural similarities with proteins from other virus families. In addition, all caliciviruses express two or three non-structural proteins for which functions have not been clearly defined. The sequence diversity of these non-structural proteins and a multitude of processing strategies suggest that at least some have evolved independently, possibly to counteract innate and adaptive immune responses in a host-specific manner. Studying these proteins is often difficult as many caliciviruses cannot be grown in cell culture. Nevertheless, the study of recombinant proteins has revealed many of their properties, such as intracellular localization, capacity to oligomerize, and ability to interact with viral and/or cellular proteins; the release of non-structural proteins from transfected cells has also been investigated. Here, we will summarize these findings and discuss recent in silico studies that identified previously overlooked putative functional domains and structural features, including transmembrane domains that suggest the presence of viroporins.

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Section: Discussionmentioning

confidence: 99%

Calicivirus Non-structural Proteins: Potential Functions in Replication and Host Cell Manipulation

et al. 2021

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“…Cat ileum- and colon-derived organoids have been published with a potential to be used as a feline coronavirus infection model ( 44 , 96 ). The establishment of rabbit intestinal organoid models have been reported using duodenal and cecal tissues ( 97 , 98 ). These models provide a useful tool in biomedical research such as studies of human bacillary dysentery, which have been facing a major challenge due to a lack of representative animal models until recent development of infant rabbit infection models ( 99 ).…”

Section: Development Of Farm and Companion Animal Organoid Models: Hi...mentioning

confidence: 99%

“…More recently, organoid-derived 2D monolayer culture models have become increasingly described in multiple animal species including pigs ( 23 , 46 , 47 , 49 – 51 , 53 , 54 , 58 , 62 , 64 ), rabbits ( 97 , 98 ), cattle ( 72 ), and dogs ( 11 ). This culture system was developed to get over the limitation of 3D culture system which arose when intestinal organoids are to be used in studies.…”

Section: Evolution Of Organoid Culture Systemsmentioning

confidence: 99%

Farm and Companion Animal Organoid Models in Translational Research: A Powerful Tool to Bridge the Gap Between Mice and Humans

Kawasaki

Goyama

Tachibana

et al. 2022

Front. Med. Technol.

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Animal organoid models derived from farm and companion animals have great potential to contribute to human health as a One Health initiative, which recognize a close inter-relationship among humans, animals and their shared environment and adopt multi-and trans-disciplinary approaches to optimize health outcomes. With recent advances in organoid technology, studies on farm and companion animal organoids have gained more attention in various fields including veterinary medicine, translational medicine and biomedical research. Not only is this because three-dimensional organoids possess unique characteristics from traditional two-dimensional cell cultures including their self-organizing and self-renewing properties and high structural and functional similarities to the originating tissue, but also because relative to conventional genetically modified or artificially induced murine models, companion animal organoids can provide an excellent model for spontaneously occurring diseases which resemble human diseases. These features of companion animal organoids offer a paradigm-shifting approach in biomedical research and improve translatability of in vitro studies to subsequent in vivo studies with spontaneously diseased animals while reducing the use of conventional animal models prior to human clinical trials. Farm animal organoids also could play an important role in investigations of the pathophysiology of zoonotic and reproductive diseases by contributing to public health and improving agricultural production. Here, we discuss a brief history of organoids and the most recent updates on farm and companion animal organoids, followed by discussion on their potential in public health, food security, and comparative medicine as One Health initiatives. We highlight recent evolution in the culturing of organoids and their integration with organ-on-a-chip systems to overcome current limitations in in vitro studies. We envision multidisciplinary work integrating organoid culture and organ-on-a-chip technology can contribute to improving both human and animal health.

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“…The medium was changed every 4 days and organoids were sub-cultured when the matrix dome became crowded. Passaging and cryopreservation of the culture was performed as described previously [31].…”

Section: Isolation and Maintenance Of 3d Rabbit Hepatobiliary Organoidsmentioning

confidence: 99%

Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses

Kardia

Fakhri

Pavy

et al. 2022

Preprint

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Lagoviruses, family Caliciviridae, are some of the most virulent vertebrate viruses known. They infect leporids, i.e., rabbits (Oryctolagus spp.), hares (Lepus spp.) and cottontails (Sylvilagus spp.) and rapidly kill over 95% of susceptible animals. Pathogenic lagoviruses are hepatotropic and induce a fulminant hepatitis that typically leads to disseminated intravascular coagulation within 24-72 hours of infection. However, the pathophysiological mechanisms governing this extreme phenotype and other aspects of the fundamental biology of these viruses are poorly understood due to a lack of cell culture systems. Here, we report on a robust and reliable ex vivo model for the cultivation of hepatotropic lagoviruses. We show that three rabbit haemorrhagic disease virus (RHDV) variants, RHDV1, RHDV2 and RHDVa-K5, replicate in monolayer cultures derived from rabbit hepatobiliary organoids. Viral replication was demonstrated by a (i) increase in viral RNA levels of greater than one log10 over a 23-hour period, (ii) detection of viral structural and non-structural proteins, and (iii) detection of double-stranded RNA viral replication intermediates. Furthermore, we generated hepatobiliary organoids from a feral cat (Felis domesticus), a wild mouse (Mus musculus) and a European brown hare (Lepus europaeus) and showed that monolayer cultures derived from the cat and mouse organoids were not permissive for lagovirus infection, while those derived from the hare organoids only supported replication of RHDV2, recapitulating the species tropism that has been observed with these viruses. Our organoid culture system will facilitate future studies into the molecular biology of lagoviruses, which will have considerable import for the conservation of endangered leporid species in Europe and North America and the biocontrol of overabundant rabbit populations in Australia and New Zealand.

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Culture and differentiation of rabbit intestinal organoids and organoid-derived cell monolayers

Cited by 19 publications

References 57 publications

Calicivirus Non-structural Proteins: Potential Functions in Replication and Host Cell Manipulation

Calicivirus Non-structural Proteins: Potential Functions in Replication and Host Cell Manipulation

Farm and Companion Animal Organoid Models in Translational Research: A Powerful Tool to Bridge the Gap Between Mice and Humans

Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses

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