Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection

Brügger, Melanie; Démoulins, Thomas; Barut, G. Tuba; Zumkehr, Béatrice; Esteves, Blandina I. Oliveira; Mehinagic, Kemal; Haas, Quentin; Schögler, Aline; Rameix‐Welti, Marie‐Anne; Eléouët, Jean François; Moehrlen, Ueli; Marti, Thomas; Schmid, Ralph A.; Summerfield, Artur; Posthaus, Horst; Ruggli, Nicolas; Hall, Sean; Alves, Marco P.

doi:10.1371/journal.ppat.1009789

Cited by 7 publications

(7 citation statements)

References 84 publications

(98 reference statements)

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“…The generation of PCLSs was done as described previously with some adaptations to human specimens 25 . Control lung tissue (preserved pulmonary architecture without emphysema or inflammation) was obtained from the distal non-tumorous areas of lung resections.…”

Section: Methodsmentioning

confidence: 99%

The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype

et al. 2022

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Variant of concern (VOC) Omicron-BA.1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization of Omicron-BA.1 in advanced primary cell culture systems and animal models are urgently needed. Here, we characterize Omicron-BA.1 and recombinant Omicron-BA.1 spike gene mutants in comparison with VOC Delta in well-differentiated primary human nasal and bronchial epithelial cells in vitro, followed by in vivo fitness characterization in hamsters, ferrets and hACE2-expressing mice, and immunized hACE2-mice. We demonstrate a spike-mediated enhancement of early replication of Omicron-BA.1 in nasal epithelial cultures, but limited replication in bronchial epithelial cultures. In hamsters, Delta shows dominance over Omicron-BA.1, and in ferrets Omicron-BA.1 infection is abortive. In hACE2-knock-in mice, Delta and a Delta spike clone also show dominance over Omicron-BA.1 and an Omicron-BA.1 spike clone, respectively. Interestingly, in naïve K18-hACE2 mice, we observe Delta spike-mediated increased replication and pathogenicity and Omicron-BA.1 spike-mediated reduced replication and pathogenicity, suggesting that the spike gene is a major determinant of replication and pathogenicity. Finally, the Omicron-BA.1 spike clone is less well-controlled by mRNA-vaccination in K18-hACE2-mice and becomes more competitive compared to the progenitor and Delta spike clones, suggesting that spike gene-mediated immune evasion is another important factor that led to Omicron-BA.1 dominance.

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Section: Methodsmentioning

confidence: 99%

The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype

et al. 2022

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“…The generation of PCLSs was done as described previously with some adaptations to human specimens 23 . Control lung tissue (preserved pulmonary architecture without emphysema or inflammation) was obtained from the distal non-tumorous areas of lung resections.…”

Section: Methodsmentioning

confidence: 99%

The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype

Barut

Halwe

Taddeo

et al. 2022

Preprint

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Variant of concern (VOC) Omicron-BA1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization of Omicron-BA.1 in advanced primary cell culture systems and multiple animal models is urgently needed. Here, we characterized Omicron-BA.1 and recombinant Omicron-BA.1 spike gene mutants in comparison with VOC Delta in well-differentiated primary human nasal and bronchial epithelial cells in vitro, followed by in vivo fitness characterization in naïve hamsters, ferrets and hACE2-expressing mice, and in immunized hACE2-mice. We demonstrate a spike-mediated enhancement of early replication of Omicron-BA.1 in nasal epithelial cultures, but limited replication in bronchial epithelial cultures. In Syrian hamsters, Delta showed dominance over Omicron-BA.1 and in ferrets, Omicron-BA.1 infection was abortive. In mice expressing the authentic hACE2-receptor, Delta and a Delta spike clone also showed dominance over Omicron-BA.1 and an Omicron-BA.1 spike clone, respectively. Interestingly, in naïve K18-hACE2 mice, we observed Delta spike-mediated increased replication and pathogenicity and Omicron-BA.1 spike-mediated reduced replication and pathogenicity, suggesting that the spike gene is a major determinant of both Delta and Omicron-BA.1 replication and pathogenicity. Finally, the Omicron-BA.1 spike clone was less well controlled by mRNA-vaccination in K18-hACE2-mice and became more competitive compared to the progenitor and Delta spike clones, suggesting that spike gene-mediated immune evasion is another important factor that led to Omicron-BA.1 dominance.

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“…OP neon/nLucP (unpublished data), wild-type CDV strain (A75/17 neon/nLucP ) ( 44 ), MeV-Edm, MeV-ICB (mentioned above), RSV-GFP ( 45 ), rNiV-EGFP ( 46 ), and PIV-5 neon/nLucP (mentioned above) have been rescued as described previously. Desired inhibitors, dissolved in DMSO, were added in a 96-well plate (Greiner Bio-One) starting at 100 nM with increasing concentration of half a log up to 100 μM.…”

Section: Methodsmentioning

confidence: 99%