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Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes

Viral entry mechanisms for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important aspect of virulence. Proposed mechanisms involve host cell membrane-bound angiotensin-converting enzyme 2 (ACE2), type II transmembrane serine proteases (TTSPs), such as transmembrane serine prot...

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Autores principales: Breidenbach, Joshua D., Dube, Prabhatchandra, Ghosh, Subhanwita, Abdullah, Belal N., Modyanov, Nikolai N., Malhotra, Deepak, Dworkin, Lance D., Haller, Steven T., Kennedy, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720121/
https://www.ncbi.nlm.nih.gov/pubmed/32992731
http://dx.doi.org/10.3390/jpm10040146
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author Breidenbach, Joshua D.
Dube, Prabhatchandra
Ghosh, Subhanwita
Abdullah, Belal N.
Modyanov, Nikolai N.
Malhotra, Deepak
Dworkin, Lance D.
Haller, Steven T.
Kennedy, David J.
author_facet Breidenbach, Joshua D.
Dube, Prabhatchandra
Ghosh, Subhanwita
Abdullah, Belal N.
Modyanov, Nikolai N.
Malhotra, Deepak
Dworkin, Lance D.
Haller, Steven T.
Kennedy, David J.
author_sort Breidenbach, Joshua D.
collection PubMed
description Viral entry mechanisms for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important aspect of virulence. Proposed mechanisms involve host cell membrane-bound angiotensin-converting enzyme 2 (ACE2), type II transmembrane serine proteases (TTSPs), such as transmembrane serine protease isoform 2 (TMPRSS2), lysosomal endopeptidase Cathepsin L (CTSL), subtilisin-like proprotein peptidase furin (FURIN), and even potentially membrane bound heparan sulfate proteoglycans. The distribution and expression of many of these genes across cell types representing multiple organ systems in healthy individuals has recently been demonstrated. However, comorbidities such as diabetes and cardiovascular disease are highly prevalent in patients with Coronavirus Disease 2019 (COVID-19) and are associated with worse outcomes. Whether these conditions contribute directly to SARS-CoV-2 virulence remains unclear. Here, we show that the expression levels of ACE2, TMPRSS2 and other viral entry-related genes, as well as potential downstream effector genes such as bradykinin receptors, are modulated in the target organs of select disease states. In tissues, such as the heart, which normally express ACE2 but minimal TMPRSS2, we found that TMPRSS2 as well as other TTSPs are elevated in individuals with comorbidities compared to healthy individuals. Additionally, we found the increased expression of viral entry-related genes in the settings of hypertension, cancer, or smoking across target organ systems. Our results demonstrate that common comorbidities may contribute directly to SARS-CoV-2 virulence and we suggest new therapeutic targets to improve outcomes in vulnerable patient populations.
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spelling pubmed-77201212020-12-08 Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes Breidenbach, Joshua D. Dube, Prabhatchandra Ghosh, Subhanwita Abdullah, Belal N. Modyanov, Nikolai N. Malhotra, Deepak Dworkin, Lance D. Haller, Steven T. Kennedy, David J. J Pers Med Article Viral entry mechanisms for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important aspect of virulence. Proposed mechanisms involve host cell membrane-bound angiotensin-converting enzyme 2 (ACE2), type II transmembrane serine proteases (TTSPs), such as transmembrane serine protease isoform 2 (TMPRSS2), lysosomal endopeptidase Cathepsin L (CTSL), subtilisin-like proprotein peptidase furin (FURIN), and even potentially membrane bound heparan sulfate proteoglycans. The distribution and expression of many of these genes across cell types representing multiple organ systems in healthy individuals has recently been demonstrated. However, comorbidities such as diabetes and cardiovascular disease are highly prevalent in patients with Coronavirus Disease 2019 (COVID-19) and are associated with worse outcomes. Whether these conditions contribute directly to SARS-CoV-2 virulence remains unclear. Here, we show that the expression levels of ACE2, TMPRSS2 and other viral entry-related genes, as well as potential downstream effector genes such as bradykinin receptors, are modulated in the target organs of select disease states. In tissues, such as the heart, which normally express ACE2 but minimal TMPRSS2, we found that TMPRSS2 as well as other TTSPs are elevated in individuals with comorbidities compared to healthy individuals. Additionally, we found the increased expression of viral entry-related genes in the settings of hypertension, cancer, or smoking across target organ systems. Our results demonstrate that common comorbidities may contribute directly to SARS-CoV-2 virulence and we suggest new therapeutic targets to improve outcomes in vulnerable patient populations. MDPI 2020-09-25 /pmc/articles/PMC7720121/ /pubmed/32992731 http://dx.doi.org/10.3390/jpm10040146 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Breidenbach, Joshua D.
Dube, Prabhatchandra
Ghosh, Subhanwita
Abdullah, Belal N.
Modyanov, Nikolai N.
Malhotra, Deepak
Dworkin, Lance D.
Haller, Steven T.
Kennedy, David J.
Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes
title Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes
title_full Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes
title_fullStr Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes
title_full_unstemmed Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes
title_short Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes
title_sort impact of comorbidities on sars-cov-2 viral entry-related genes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720121/
https://www.ncbi.nlm.nih.gov/pubmed/32992731
http://dx.doi.org/10.3390/jpm10040146
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