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The role of high cholesterol in SARS-CoV-2 infectivity

Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2. The virus binds to angiotensinogen converting enzyme 2 (ACE2), which mediates viral entry into mammalian cells. COVID-19 is notably severe in the elderly and in those with underl...

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Autores principales: Wang, Hao, Yuan, Zixuan, Pavel, Mahmud Arif, Jablonski, Sonia Mediouni, Jablonski, Joseph, Hobson, Robert, Valente, Susana, Reddy, Chakravarthy B., Hansen, Scott B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140059/
https://www.ncbi.nlm.nih.gov/pubmed/37119851
http://dx.doi.org/10.1016/j.jbc.2023.104763
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author Wang, Hao
Yuan, Zixuan
Pavel, Mahmud Arif
Jablonski, Sonia Mediouni
Jablonski, Joseph
Hobson, Robert
Valente, Susana
Reddy, Chakravarthy B.
Hansen, Scott B.
author_facet Wang, Hao
Yuan, Zixuan
Pavel, Mahmud Arif
Jablonski, Sonia Mediouni
Jablonski, Joseph
Hobson, Robert
Valente, Susana
Reddy, Chakravarthy B.
Hansen, Scott B.
author_sort Wang, Hao
collection PubMed
description Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2. The virus binds to angiotensinogen converting enzyme 2 (ACE2), which mediates viral entry into mammalian cells. COVID-19 is notably severe in the elderly and in those with underlying chronic conditions. The cause of selective severity is not well understood. Here we show cholesterol and the signaling lipid phosphatidyl-inositol 4,5 bisphosphate (PIP(2)) regulate viral infectivity through the localization of ACE2’s into nanoscopic (<200 nm) lipid clusters. Uptake of cholesterol into cell membranes (a condition common to chronic disease) causes ACE2 to move from PIP(2) lipids to endocytic ganglioside (GM1) lipids, where the virus is optimally located for viral entry. In mice, age and high-fat diet increase lung tissue cholesterol by up to 40%. And in smokers with chronic disease, cholesterol is elevated 2-fold, a magnitude of change that dramatically increases infectivity of virus in cell culture. We conclude increasing the ACE2 location near endocytic lipids increases viral infectivity and may help explain the selective severity of COVID-19 in aged and diseased populations.
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spelling pubmed-101400592023-04-28 The role of high cholesterol in SARS-CoV-2 infectivity Wang, Hao Yuan, Zixuan Pavel, Mahmud Arif Jablonski, Sonia Mediouni Jablonski, Joseph Hobson, Robert Valente, Susana Reddy, Chakravarthy B. Hansen, Scott B. J Biol Chem Research Article Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2. The virus binds to angiotensinogen converting enzyme 2 (ACE2), which mediates viral entry into mammalian cells. COVID-19 is notably severe in the elderly and in those with underlying chronic conditions. The cause of selective severity is not well understood. Here we show cholesterol and the signaling lipid phosphatidyl-inositol 4,5 bisphosphate (PIP(2)) regulate viral infectivity through the localization of ACE2’s into nanoscopic (<200 nm) lipid clusters. Uptake of cholesterol into cell membranes (a condition common to chronic disease) causes ACE2 to move from PIP(2) lipids to endocytic ganglioside (GM1) lipids, where the virus is optimally located for viral entry. In mice, age and high-fat diet increase lung tissue cholesterol by up to 40%. And in smokers with chronic disease, cholesterol is elevated 2-fold, a magnitude of change that dramatically increases infectivity of virus in cell culture. We conclude increasing the ACE2 location near endocytic lipids increases viral infectivity and may help explain the selective severity of COVID-19 in aged and diseased populations. American Society for Biochemistry and Molecular Biology 2023-04-28 /pmc/articles/PMC10140059/ /pubmed/37119851 http://dx.doi.org/10.1016/j.jbc.2023.104763 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Wang, Hao
Yuan, Zixuan
Pavel, Mahmud Arif
Jablonski, Sonia Mediouni
Jablonski, Joseph
Hobson, Robert
Valente, Susana
Reddy, Chakravarthy B.
Hansen, Scott B.
The role of high cholesterol in SARS-CoV-2 infectivity
title The role of high cholesterol in SARS-CoV-2 infectivity
title_full The role of high cholesterol in SARS-CoV-2 infectivity
title_fullStr The role of high cholesterol in SARS-CoV-2 infectivity
title_full_unstemmed The role of high cholesterol in SARS-CoV-2 infectivity
title_short The role of high cholesterol in SARS-CoV-2 infectivity
title_sort role of high cholesterol in sars-cov-2 infectivity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140059/
https://www.ncbi.nlm.nih.gov/pubmed/37119851
http://dx.doi.org/10.1016/j.jbc.2023.104763
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