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Article

Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice

Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Andrew Davidson
Viruses 2021, 13(1), 132; https://doi.org/10.3390/v13010132
Received: 14 December 2020 / Revised: 8 January 2021 / Accepted: 12 January 2021 / Published: 19 January 2021
(This article belongs to the Special Issue Pathogenesis of Human and Animal Coronaviruses)
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can cause neurological disease in humans, but little is known about the pathogenesis of SARS-CoV-2 infection in the central nervous system (CNS). Herein, using K18-hACE2 mice, we demonstrate that SARS-CoV-2 neuroinvasion and encephalitis is associated with mortality in these mice. Intranasal infection of K18-hACE2 mice with 105 plaque-forming units of SARS-CoV-2 resulted in 100% mortality by day 6 after infection. The highest virus titers in the lungs were observed on day 3 and declined on days 5 and 6 after infection. By contrast, very high levels of infectious virus were uniformly detected in the brains of all the animals on days 5 and 6. Onset of severe disease in infected mice correlated with peak viral levels in the brain. SARS-CoV-2-infected mice exhibited encephalitis hallmarks characterized by production of cytokines and chemokines, leukocyte infiltration, hemorrhage and neuronal cell death. SARS-CoV-2 was also found to productively infect cells within the nasal turbinate, eye and olfactory bulb, suggesting SARS-CoV-2 entry into the brain by this route after intranasal infection. Our data indicate that direct infection of CNS cells together with the induced inflammatory response in the brain resulted in the severe disease observed in SARS-CoV-2-infected K18-hACE2 mice. View Full-Text
Keywords: SARS-CoV-2; COVID-19; K18-hACE2 mice; neuroinvasion; neuroinflammation; encephalitis SARS-CoV-2; COVID-19; K18-hACE2 mice; neuroinvasion; neuroinflammation; encephalitis
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MDPI and ACS Style

Kumari, P.; Rothan, H.A.; Natekar, J.P.; Stone, S.; Pathak, H.; Strate, P.G.; Arora, K.; Brinton, M.A.; Kumar, M. Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice. Viruses 2021, 13, 132. https://0-doi-org.brum.beds.ac.uk/10.3390/v13010132

AMA Style

Kumari P, Rothan HA, Natekar JP, Stone S, Pathak H, Strate PG, Arora K, Brinton MA, Kumar M. Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice. Viruses. 2021; 13(1):132. https://0-doi-org.brum.beds.ac.uk/10.3390/v13010132

Chicago/Turabian Style

Kumari, Pratima; Rothan, Hussin A.; Natekar, Janhavi P.; Stone, Shannon; Pathak, Heather; Strate, Philip G.; Arora, Komal; Brinton, Margo A.; Kumar, Mukesh. 2021. "Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice" Viruses 13, no. 1: 132. https://0-doi-org.brum.beds.ac.uk/10.3390/v13010132

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