SARS-CoV-2 Infectivity and Neurological Targets in the Brain
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ORIGINAL RESEARCH
SARS‑CoV‑2 Infectivity and Neurological Targets in the Brain Walter J. Lukiw1,2,3,4,7 · Aileen Pogue2 · James M. Hill1,4,5,6 Received: 15 June 2020 / Accepted: 14 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The gateway for invasion by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human host cells is via the angiotensin-converting enzyme 2 (ACE2) transmembrane receptor expressed in multiple immune and nonimmune cell types. SARS-CoV-2, that causes coronavirus disease 2019 (COVID-19; CoV-19) has the unusual capacity to attack many different types of human host cells simultaneously via novel clathrin- and caveolae-independent endocytic pathways, becoming injurious to diverse cells, tissues and organ systems and exploiting any immune weakness in the host. The elicitation of this multipronged attack explains in part the severity and extensive variety of signs and symptoms observed in CoV-19 patients. To further our understanding of the mechanism and pathways of SARS-CoV-2 infection and susceptibility of specific cell- and tissue-types and organ systems to SARS-CoV-2 attack in this communication we analyzed ACE2 expression in 85 human tissues including 21 different brain regions, 7 fetal tissues and 8 controls. Besides strong ACE2 expression in respiratory, digestive, renal-excretory and reproductive cells, high ACE2 expression was also found in the amygdala, cerebral cortex and brainstem. The highest ACE2 expression level was found in the pons and medulla oblongata in the human brainstem, containing the medullary respiratory centers of the brain, and may in part explain the susceptibility of many CoV-19 patients to severe respiratory distress. Keywords Alzheimer’s disease · Angiotensin-converting enzyme 2 (ACE2) receptor · Coronavirus · COVID-19 · CoV-19 · Hartnup’s disease · microRNA · miRNA-5197 · SARS-CoV-2 · single stranded RNA (ssRNA) For interested readers and ACE2-CoV-19 researchers key updated website links, excellently presented, regarding multiple aspects of ACE2 expression, SARS-CoV-2 invasion and CoV-19 disease can be found at: https://genome.ucsc.edu/covid19.html (COVID-19 Pandemic Resources at UCSC); https://www.rndsystems. com/resources/articles/ace-2-sars-receptor-identified (ACE2: The Receptor for SARS-CoV-2); https://academic.oup.com/ eurheartj/article/26/4/322/439241 (ACE and ACE2: a tale of two enzymes, from the European Hearth Journal 2005); and https:// medicalxpress.com/news/2020–05-ace2-receptor-coronavirus. html (What is the ACE2 receptor, and how is it connected to coronavirus? From the Medical Express, 2020).
Introduction
* Walter J. Lukiw [email protected]
5
Department of Pharmacology, LSU Health Science Center, New Orleans, LA 70112‑2272, USA
6
Department of Microbiology, LSU Health Science Center, New Orleans, LA 70112‑2272, USA
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Department of Neuroscience, Neurology and Ophthalmology, Bollinger Professor of Alzheimer’s Disease, LSU Neuroscience Center of Excellence, Louisiana
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