SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids
The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation is retained for later variants like BA.5 and XBB remains controversial. We show that BA.5 and XBB isolates were significantly more pathogenic in K18-hACE2 mice...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1320856/full |
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| author | Romal Stewart Kexin Yan Sevannah A. Ellis Cameron R. Bishop Troy Dumenil Bing Tang Wilson Nguyen Thibaut Larcher Rhys Parry Julian De Jun Sng Alexander A. Khromykh Alexander A. Khromykh Robert K. P. Sullivan Mary Lor Frédéric A. Meunier Frédéric A. Meunier Daniel J. Rawle Andreas Suhrbier Andreas Suhrbier |
| author_facet | Romal Stewart Kexin Yan Sevannah A. Ellis Cameron R. Bishop Troy Dumenil Bing Tang Wilson Nguyen Thibaut Larcher Rhys Parry Julian De Jun Sng Alexander A. Khromykh Alexander A. Khromykh Robert K. P. Sullivan Mary Lor Frédéric A. Meunier Frédéric A. Meunier Daniel J. Rawle Andreas Suhrbier Andreas Suhrbier |
| author_sort | Romal Stewart |
| collection | DOAJ |
| description | The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation is retained for later variants like BA.5 and XBB remains controversial. We show that BA.5 and XBB isolates were significantly more pathogenic in K18-hACE2 mice than a BA.1 isolate, showing increased neurotropic potential, resulting in fulminant brain infection and mortality, similar to that seen for original ancestral isolates. BA.5 also infected human cortical brain organoids to a greater extent than the BA.1 and original ancestral isolates. In the brains of mice, neurons were the main target of infection, and in human organoids neuronal progenitor cells and immature neurons were infected. The results herein suggest that evolving omicron variants may have increasing neurotropic potential. |
| first_indexed | 2024-03-10T03:25:50Z |
| format | Article |
| id | doaj.art-e3bb846c283046a5ad1923ef2b19de68 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-10T03:25:50Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-e3bb846c283046a5ad1923ef2b19de682023-11-23T09:53:56ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-11-011410.3389/fmicb.2023.13208561320856SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoidsRomal Stewart0Kexin Yan1Sevannah A. Ellis2Cameron R. Bishop3Troy Dumenil4Bing Tang5Wilson Nguyen6Thibaut Larcher7Rhys Parry8Julian De Jun Sng9Alexander A. Khromykh10Alexander A. Khromykh11Robert K. P. Sullivan12Mary Lor13Frédéric A. Meunier14Frédéric A. Meunier15Daniel J. Rawle16Andreas Suhrbier17Andreas Suhrbier18QIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, University of Queensland, Brisbane, QLD, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaINRAE, Oniris, PAnTher, APEX, Nantes, FranceSchool of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD, AustraliaSchool of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD, AustraliaSchool of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD, AustraliaGVN Centre of Excellence, Australian Infectious Disease Research Centre, Brisbane, QLD, AustraliaClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, University of Queensland, Brisbane, QLD, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, University of Queensland, Brisbane, QLD, AustraliaGVN Centre of Excellence, Australian Infectious Disease Research Centre, Brisbane, QLD, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaGVN Centre of Excellence, Australian Infectious Disease Research Centre, Brisbane, QLD, AustraliaThe reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation is retained for later variants like BA.5 and XBB remains controversial. We show that BA.5 and XBB isolates were significantly more pathogenic in K18-hACE2 mice than a BA.1 isolate, showing increased neurotropic potential, resulting in fulminant brain infection and mortality, similar to that seen for original ancestral isolates. BA.5 also infected human cortical brain organoids to a greater extent than the BA.1 and original ancestral isolates. In the brains of mice, neurons were the main target of infection, and in human organoids neuronal progenitor cells and immature neurons were infected. The results herein suggest that evolving omicron variants may have increasing neurotropic potential.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1320856/fullSARS-CoV-2omicronXBBBA.5K18-hACE2brain |
| spellingShingle | Romal Stewart Kexin Yan Sevannah A. Ellis Cameron R. Bishop Troy Dumenil Bing Tang Wilson Nguyen Thibaut Larcher Rhys Parry Julian De Jun Sng Alexander A. Khromykh Alexander A. Khromykh Robert K. P. Sullivan Mary Lor Frédéric A. Meunier Frédéric A. Meunier Daniel J. Rawle Andreas Suhrbier Andreas Suhrbier SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids Frontiers in Microbiology SARS-CoV-2 omicron XBB BA.5 K18-hACE2 brain |
| title | SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids |
| title_full | SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids |
| title_fullStr | SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids |
| title_full_unstemmed | SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids |
| title_short | SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids |
| title_sort | sars cov 2 omicron ba 5 and xbb variants have increased neurotropic potential over ba 1 in k18 hace2 mice and human brain organoids |
| topic | SARS-CoV-2 omicron XBB BA.5 K18-hACE2 brain |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1320856/full |
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