Role of Epithelial-Endothelial Cell Interaction in the Pathogenesis of SARS-CoV-2 Infection

Scientists measured the susceptibility to infection, immune response, and expression of adhesion molecules, in human pulmonary microvascular endothelial cells exposed to conditioned medium from infected epithelial cells.
[Clinical Infectious Diseases]
Hui, K. P.-Y., Cheung, M.-C., Lai, K.-L., Ng, K.-C., Ho, J. C.-W., Peiris, M., Nicholls, J. M., & Chan, M. C.-W. (2021). Role of epithelial-endothelial cell interaction in the pathogenesis of SARS-CoV-2 infection. Clinical Infectious Diseases, ciab406. https://doi.org/10.1093/cid/ciab406 Cite
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The Furin Cleavage Site in the SARS-CoV-2 Spike Protein Is Required for Transmission in Ferrets

Investigators showed that the polybasic insertion endows SARS-CoV-2 with a selective advantage in lung cells and primary human airway epithelial cells, but impaired replication in Vero E6, a cell line used for passaging SARS-CoV-2.
[Nature Microbiology]
Peacock, T. P., Goldhill, D. H., Zhou, J., Baillon, L., Frise, R., Swann, O. C., Kugathasan, R., Penn, R., Brown, J. C., Sanchez-David, R. Y., Braga, L., Williamson, M. K., Hassard, J. A., Staller, E., Hanley, B., Osborn, M., Giacca, M., Davidson, A. D., Matthews, D. A., & Barclay, W. S. (2021). The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nature Microbiology, 1–11. https://doi.org/10.1038/s41564-021-00908-w Cite
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Experimental and Natural Evidence of SARS-CoV-2 Infection-Induced Activation of Type I Interferon Responses

Scientists demonstrated that SARS-CoV-2 infection induces a type I IFN response in vitro and in moderate cases of COVID-19.
[iScience]
Banerjee, A., El-Sayes, N., Budylowski, P., Jacob, R. A., Richard, D., Maan, H., Aguiar, J. A., Demian, W. L., Baid, K., D’Agostino, M. R., Ang, J. C., Murdza, T., Tremblay, B. J.-M., Afkhami, S., Karimzadeh, M., Irving, A. T., Yip, L., Ostrowski, M., Hirota, J. A., … Mossman, K. (2021). Experimental and natural evidence of SARS-CoV-2 infection-induced activation of type I interferon responses. IScience, 0(0). https://doi.org/10.1016/j.isci.2021.102477 Cite
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Structure-Based Phylogeny Identifies Avoralstat as a TMPRSS2 Inhibitor That Prevents SARS-CoV-2 Infection in Mice

Scientists created a structure-based phylogenetic computational tool named 3DPhyloFold to systematically identify structurally similar serine proteases with known therapeutic inhibitors and demonstrated effective inhibition of SARS-CoV-2 infection in vitro and in vivo.
[Journal of Clinical Investigation]
Sun, Y. J., Velez, G., Parsons, D. E., Li, K., Ortiz, M. E., Sharma, S., Jr, P. B. M., Bassuk, A. G., & Mahajan, V. B. (2021). Structure-based phylogeny identifies Avoralstat as a TMPRSS2 inhibitor that prevents SARS-CoV-2 infection in mice. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI147973 Cite
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Disparate Temperature-Dependent Virus–Host Dynamics for SARS-CoV-2 and SARS-CoV in the Human Respiratory Epithelium

Since different temperatures encountered in the human upper and lower respiratory tract have been shown to affect the replication kinetics of several respiratory viruses, as well as host immune response dynamics, scientists investigated the impact of temperatures during SARS-CoV-2 and SARS-CoV infection using the primary human airway epithelial cell culture model.
[PLoS Biology]
V’kovski, P., Gultom, M., Kelly, J. N., Steiner, S., Russeil, J., Mangeat, B., Cora, E., Pezoldt, J., Holwerda, M., Kratzel, A., Laloli, L., Wider, M., Portmann, J., Tran, T., Ebert, N., Stalder, H., Hartmann, R., Gardeux, V., Alpern, D., … Dijkman, R. (2021). Disparate temperature-dependent virus–host dynamics for SARS-CoV-2 and SARS-CoV in the human respiratory epithelium. PLOS Biology, 19(3), e3001158. https://doi.org/10.1371/journal.pbio.3001158 Cite
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LasR-Deficient Pseudomonas Aeruginosa Variants Increase Airway Epithelial mICAM-1 Expression and Enhance Neutrophilic Lung Inflammation

Scientists investigated how lasR mutants modulate airway epithelial membrane bound mICAM-1, a surface adhesion molecule, and determined its impact on neutrophilic inflammation in vitro and in vivo.
[PLoS Pathogens]
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The In Vitro Multilineage Differentiation and Maturation of Lung and Airway Cells from Human Pluripotent Stem Cell–Derived Lung Progenitors in 3D

Researchers describe a strategy for directed differentiation of hPSCs into mature lung and airway epithelial cells obtained through maturation of NKX2.1+ hPSC-derived lung progenitors in a 3D matrix of collagen I in the absence of glycogen synthase kinase 3 inhibition.
[Nature Protocols]
Rodrigues Toste de Carvalho, A. L., Liu, H.-Y., Chen, Y.-W., Porotto, M., Moscona, A., & Snoeck, H.-W. (2021). The in vitro multilineage differentiation and maturation of lung and airway cells from human pluripotent stem cell–derived lung progenitors in 3D. Nature Protocols, 1–28. https://doi.org/10.1038/s41596-020-00476-z Cite
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