SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport.
Am J Physiol Lung Cell Mol Physiol
; 320(3): L430-L435, 2021 03 01.
Article
em En
| MEDLINE
| ID: mdl-33434105
ABSTRACT
The tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic, toward the host cells is determined, at least in part, by the expression and distribution of its cell surface receptor, angiotensin-converting enzyme 2 (ACE2). The virus further exploits the host cellular machinery to gain access into the cells; its spike protein is cleaved by a host cell surface transmembrane serine protease 2 (TMPRSS2) shortly after binding ACE2, followed by its proteolytic activation at a furin cleavage site. The virus primarily targets the epithelium of the respiratory tract, which is covered by a tightly regulated airway surface liquid (ASL) layer that serves as a primary defense mechanism against respiratory pathogens. The volume and viscosity of this fluid layer is regulated and maintained by a coordinated function of different transport pathways in the respiratory epithelium. We argue that SARS-CoV-2 may potentially alter evolutionary conserved second-messenger signaling cascades via activation of G protein-coupled receptors (GPCRs) or by directly modulating G protein signaling. Such signaling may in turn adversely modulate transepithelial transport processes, especially those involving cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial Na+ channel (ENaC), thereby shifting the delicate balance between anion secretion and sodium absorption, which controls homeostasis of this fluid layer. As a result, activation of the secretory pathways including CFTR-mediated Cl- transport may overwhelm the absorptive pathways, such as ENaC-dependent Na+ uptake, and initiate a pathophysiological cascade leading to lung edema, one of the most serious and potentially deadly clinical manifestations of COVID-19.
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Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
4_TD
Base de dados:
MEDLINE
Assunto principal:
Receptores Acoplados a Proteínas G
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SARS-CoV-2
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COVID-19
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Pulmão
Limite:
Humans
Idioma:
En
Revista:
Am J Physiol Lung Cell Mol Physiol
Ano de publicação:
2021
Tipo de documento:
Article