Seehusen, Frauke, Clark, Jordan J, Sharma, Parul, Bentley, Eleanor G, Kirby, Adam, Subramaniam, Krishanthi, Wunderlin-Giuliani, Sabina, Hughes, Grant L, Patterson, Edward I, Michael, Benedict D 
ORCID: 0000-0002-8693-8926 et al (show 4 more authors)
(2022)
Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse.
VIRUSES-BASEL, 14 (5).
1020-.
|
Text
Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse.pdf - Published version Download (3MB) | Preview |
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) not only affects the respiratory tract but also causes neurological symptoms such as loss of smell and taste, headache, fatigue or severe cerebrovascular complications. Using transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2), we investigated the spatiotemporal distribution and pathomorphological features in the CNS following intranasal infection with SARS-CoV-2 variants, as well as after prior influenza A virus infection. Apart from Omicron, we found all variants to frequently spread to and within the CNS. Infection was restricted to neurons and appeared to spread from the olfactory bulb mainly in basally oriented regions in the brain and into the spinal cord, independent of ACE2 expression and without evidence of neuronal cell death, axonal damage or demyelination. However, microglial activation, microgliosis and a mild macrophage and T cell dominated inflammatory response was consistently observed, accompanied by apoptotic death of endothelial, microglial and immune cells, without their apparent infection. Microgliosis and immune cell apoptosis indicate a potential role of microglia for pathogenesis and viral effect in COVID-19 and the possible impairment of neurological functions, especially in long COVID. These data may also be informative for the selection of therapeutic candidates and broadly support the investigation of agents with adequate penetration into relevant regions of the CNS.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Severe Acute Respiratory Syndrome Coronavirus 2, mouse model, COVID-19, encephalitis, microgliosis, influenza A virus coinfection, virus variants |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 10 Jun 2022 14:11 |
| Last Modified: | 18 Jan 2023 21:00 |
| DOI: | 10.3390/v14051020 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3156187 |
Dimensions
Dimensions
