Louis Pasteur continues to shape the future of microbiology DOI Creative Commons
Serge Mostowy

Disease Models & Mechanisms, Journal Year: 2022, Volume and Issue: 15(12)

Published: Dec. 1, 2022

Louis Pasteur made seminal discoveries in microbiology, immunology and vaccinology that transformed clinical science saved millions of lives. Since the 19th century, our ability to study infectious disease has undergone radical changes due newly emerging technologies infection models. In this Editorial, I consider Pasteur's impact on understand combat context two modern-day pandemics: coronavirus 2019 (COVID-19) antimicrobial resistance (AMR). During COVID-19 pandemic, we witnessed remarkable ambition severe acute respiratory syndrome 2 (SARS-CoV-2) innovate effective vaccines prevent disease. For comparatively overlooked pandemic AMR, require same level urgency develop alternative approaches antibiotic-resistant bacterial strains cause deaths annually. statement "chance only favours mind which is prepared" a principle captures 'l'esprit Pasteur'. This should continue guide research disease, for need support development predictive models cutting-edge mechanistic prepare us discovery therapeutic impact.

Language: Английский

SARS-CoV-2 pathogenesis DOI Open Access
Mart M. Lamers, Bart L. Haagmans

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 20(5), P. 270 - 284

Published: March 30, 2022

Language: Английский

Citations

702
Human organoids: New strategies and methods for analyzing human development and disease DOI Creative Commons
Nina S. Corsini, Juergen A. Knoblich

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2756 - 2769

Published: July 1, 2022

For decades, insight into fundamental principles of human biology and disease has been obtained primarily by experiments in animal models. While this allowed researchers to understand many biological processes great detail, some developmental mechanisms have proven difficult study due inherent species differences. The advent organoid technology more than 10 years ago established laboratory-grown organ tissues as an additional model system recapitulate human-specific aspects biology. use 3D organoids, well other advances single-cell technologies, revealed unprecedented insights mechanisms, especially those that distinguish humans from species. This review highlights novel with a focus on how generated better understanding development disease.

Language: Английский

Citations

96
3D organ-on-a-chip: The convergence of microphysiological systems and organoids DOI Creative Commons
Leandra Santos Baptista, Constance Porrini, Gabriela S. Kronemberger

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Nov. 21, 2022

Medicine today faces the combined challenge of an increasing number untreatable diseases and fewer drugs reaching clinic. While pharmaceutical companies have increased in early development entering phase I clinical trials, actually successfully pass III launch into market. In fact, only 1 out every 9 will launch.

Language: Английский

Citations

50
Choosing a cellular model to study SARS-CoV-2 DOI Creative Commons
Gabriel Augusto Pires de Souza,

Marion Le Bideau,

Céline Boschi

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: Oct. 21, 2022

As new pathogens emerge, challenges must be faced. This is no different in infectious disease research, where identifying the best tools available laboratories to conduct an investigation can, at least initially, particularly complicated. However, context of emerging virus, such as SARS-CoV-2, which was recently detected China and has become a global threat healthcare systems, developing models infection pathogenesis urgently required. Cell-based approaches are crucial understanding coronavirus biology, growth kinetics, tropism. Usually, laboratory cell lines first line experimental study viral pathogenicity perform assays aimed screening antiviral compounds efficient blocking replication viruses, saving time resources, reducing use animals. determining ideal type can challenging, especially when several researchers have adapt their studies specific requirements. review strives guide scientists who venturing into studying SARS-CoV-2 help them choose right cellular models. It revisits basic concepts virology presents currently

Language: Английский

Citations

43
In Vitro Modelling of Respiratory Virus Infections in Human Airway Epithelial Cells – A Systematic Review DOI Creative Commons
Laurine C. Rijsbergen, Laura L.A. van Dijk, Maarten F. M. Engel

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 18, 2021

Respiratory tract infections (RTI) are a major cause of morbidity and mortality in humans. A large number RTIs is caused by viruses, often resulting more severe disease infants, elderly the immunocompromised. Upon viral infection, most individuals experience common cold-like symptoms associated with an upper RTI. However, some cases sometimes life-threatening lower RTI may develop. Reproducible scalable vitro culture models that accurately reflect human respiratory needed to study interactions between viruses host, test novel therapeutic interventions. Multiple cell systems have been described, but majority these based on immortalized lines. Although useful for studying certain aspects infections, such monomorphic, unicellular fall short creating understanding processes occur at integrated tissue level. Novel involving primary airway epithelial cells and, recently, organoids, now use. In this review, we describe evolution their characteristics context RTIs, starting from advances after cultures recently developed organoid systems. Furthermore, how used virus-host interactions, e.g. tropism receptor studies as well innate immune system. Finally, provide outlook future developments field, including co-factors mimic microenvironment tract.

Language: Английский

Citations

44
SARS-CoV-2 Variants of Concern Hijack IFITM2 for Efficient Replication in Human Lung Cells DOI Creative Commons
Rayhane Nchioua,

Annika Schundner,

Dorota Kmieć

et al.

Journal of Virology, Journal Year: 2022, Volume and Issue: 96(11)

Published: May 11, 2022

It has recently been shown that an early SARS-CoV-2 isolate (NL-02-2020) hijacks interferon-induced transmembrane proteins (IFITMs) for efficient replication in human lung cells, cardiomyocytes, and gut organoids. To date, several "variants of concern" (VOCs) showing increased infectivity resistance to neutralization have emerged globally replaced the viral strains. Here, we determined whether five current VOCs (Alpha, Beta, Gamma, Delta, Omicron) maintained dependency on IFITM replication. We found depletion IFITM2 strongly reduces RNA production by all epithelial cancer cell line Calu-3. Silencing IFITM1 had modest effects, while knockdown IFITM3 resulted intermediate phenotype. Strikingly, generally reduced infectious virus more than 4 orders magnitude. In addition, antibody directed against N terminus inhibited VOC induced pluripotent stem (iPSC)-derived alveolar type II thought represent major target cells lung. conclusion, endogenously expressed (especially IFITM2) are critical cofactors genuine VOCs, including currently dominant Omicron variant.

Language: Английский

Citations

32
Human Organotypic Airway and Lung Organoid Cells of Bronchiolar and Alveolar Differentiation Are Permissive to Infection by Influenza and SARS-CoV-2 Respiratory Virus DOI Creative Commons

Camilla T. Ekanger,

Fan Zhou, Dana Bohan

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: March 14, 2022

The ongoing coronavirus disease 2019 (COVID-19) pandemic has led to the initiation of unprecedented research efforts understand pathogenesis mediated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). More knowledge is needed regarding cell type-specific cytopathology and its impact on cellular tropism. Furthermore, novel SARS-CoV-2 mutations tropism, alternative routes entry, co-infections, virus replication kinetics along respiratory tract remains be explored in improved models. Most applied virology models are not well suited address remaining questions, as they do recapitulate histoarchitecture composition human tissues. overall aim this work was establish from single biopsy specimens, a adult stem cell-derived organoid model representing upper airways lungs explore applicability study infection. First, we characterized with respect growth pattern histoarchitecture, composition, functional characteristics. Next, situ expression viral entry receptors, including influenza virus-relevant sialic acids receptor ACE2 TMPRSS2, were confirmed organoids bronchiolar alveolar differentiation. We further showed successful infection pseudotype A H7N1 H5N1 virus, ability support virus. Finally, clinical isolate TCID50 assay immunostaining detect intracellular specific nucleocapsid dsRNA. prominent syncytia formation tissues following mimics findings infected . conclude that organotypic described here may particularly useful for studies evaluate regional differences host response contains various types tract, expresses factors, supports SARS-CoV-2. Thus, serve relevant reliable tool aid preparedness, efficient evaluation antiviral strategies.

Language: Английский

Citations

30
Air-Liquid-Interface Differentiated Human Nose Epithelium: A Robust Primary Tissue Culture Model of SARS-CoV-2 Infection DOI Open Access
Bang M. Tran, Samantha L. Grimley, Julie McAuley

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(2), P. 835 - 835

Published: Jan. 13, 2022

The global urgency to uncover medical countermeasures combat the COVID-19 pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has revealed an unmet need for robust tissue culture models that faithfully recapitulate key features of human tissues and disease. Infection nose is considered dominant initial site SARS-CoV-2 infection replicate this entry portal offer greatest potential examining demonstrating effectiveness designed prevent or manage highly communicable Here, we test air–liquid-interface (ALI) differentiated nasal epithelium (HNE) system as a model authentic infection. Progenitor cells (basal cells) were isolated from turbinate brushings, expanded under conditionally reprogrammed cell (CRC) conditions at ALI. Differentiated inoculated with different clinical isolates. Infectious virus release into apical washes was determined TCID50, while infected visualized immunofluorescence confocal microscopy. We demonstrate robust, reproducible ALI-HNE established donors. Viral occurred surface, primarily observed in ciliated cells. In contrast ancestral isolate, Delta variant considerable damage. Successful establishment donor dependent. can serve pre-clinical without invasive collection samples.

Language: Английский

Citations

28
Harnessing three-dimensional (3D) cell culture models for pulmonary infections: State of the art and future directions DOI Open Access
Disha D. Shah, Neha R. Raghani, Mehul R. Chorawala

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2023, Volume and Issue: 396(11), P. 2861 - 2880

Published: June 2, 2023

Language: Английский

Citations

19
Host Response of Syrian Hamster to SARS-CoV-2 Infection including Differences with Humans and between Sexes DOI Creative Commons

Martina Castellan,

Gianpiero Zamperin, Giulia Franzoni

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 428 - 428

Published: Feb. 3, 2023

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the importance having proper tools and models to study pathophysiology emerging infectious diseases test therapeutic protocols, assess changes in viral phenotypes, evaluate effects evolution. This provided a comprehensive characterization Syrian hamster (Mesocricetus auratus) as an animal model for SARS-CoV-2 infection using different approaches (description clinical signs, load, receptor profiling, host immune response) targeting four organs (lungs, intestine, brain, PBMCs). Our data showed that both male female hamsters were susceptible developed disease similar one observed patients with COVID-19 included moderate pulmonary lesions, inflammation, recruitment system lungs at systemic level. However, all animals recovered within 14 days without developing pathology seen humans, none them died. We found faint evidence intestinal neurological tropism associated absence lesions minimal response intestines brains, which another crucial difference multiorgan impairment COVID-19. When comparing hamsters, we males sustained higher RNA shedding replication lungs, suffered from more symptoms histopathological triggered inflammation. Overall, these confirmed suitable mild reflected sex-related differences against virus humans.

Language: Английский

Citations

17