Does SARS‐Cov‐2 invade the brain? Translational lessons from animal models
- 22 May 2020
- journal article
- review article
- Published by Wiley in European Journal of Neurology
- Vol. 27 (9), 1764-1773
- https://doi.org/10.1111/ene.14277
Abstract
The current coronavirus disease (COVID-19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS-CoV-2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS-CoV-2. One key finding that may unify these pathogens is that all require angiotensin-converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS-CoV-2 binds to cell membranes, binds angiotensin-converting enzyme 2 with a higher affinity compared with SARS-CoV. The expression of this receptor in neurons and endothelial cells hints that SARS-CoV-2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune-mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune-mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID-19.This publication has 55 references indexed in Scilit:
- Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4Cell Research, 2013
- Tropism of and Innate Immune Responses to the Novel Human Betacoronavirus Lineage C Virus in Human Ex Vivo Respiratory Organ CulturesJournal of Virology, 2013
- Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune ResponseJournal of Virology, 2011
- Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2Journal of Virology, 2008
- Lethal Infection of K18- hACE2 Mice Infected with Severe Acute Respiratory Syndrome CoronavirusJournal of Virology, 2007
- Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin systemAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007
- Interaction of severe acute respiratory syndrome-associated coronavirus with dendritic cellsJournal of General Virology, 2006
- Susceptibility of human and rat neural cell lines to infection by SARS-coronavirusBiochemical and Biophysical Research Communications, 2005
- Multiple organ infection and the pathogenesis of SARSThe Journal of Experimental Medicine, 2005
- Hemoglobin in Samples with Leukocytosis Can Be Measured on ABL 700 Series Blood Gas AnalyzersClinical Chemistry, 2003