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SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids

Authors :
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
Robert K. P. Sullivan
Mary Lor
Frédéric A. Meunier
Daniel J. Rawle
Andreas Suhrbier
Source :
Frontiers in Microbiology, Vol 14 (2023)
Publication Year :
2023
Publisher :
Frontiers Media S.A., 2023.

Abstract

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.

Details

Language :
English
ISSN :
1664302X
Volume :
14
Database :
Directory of Open Access Journals
Journal :
Frontiers in Microbiology
Publication Type :
Academic Journal
Accession number :
edsdoj.3bb846c283046a5ad1923ef2b19de68
Document Type :
article
Full Text :
https://doi.org/10.3389/fmicb.2023.1320856