Pneumocytes are distinguished by highly elevated expression of the ER stress biomarker GRP78, a co-receptor for SARS-CoV-2, in COVID-19 autopsies.
Adult
Aged
Aged, 80 and over
Alveolar Epithelial Cells
/ metabolism
Autopsy
COVID-19
/ metabolism
Case-Control Studies
Endoplasmic Reticulum Chaperone BiP
Endoplasmic Reticulum Stress
Female
Heat-Shock Proteins
/ analysis
Host-Pathogen Interactions
Humans
Macrophages, Alveolar
/ metabolism
Male
Middle Aged
Proteostasis
Receptors, Coronavirus
/ analysis
SARS-CoV-2
/ pathogenicity
Up-Regulation
Young Adult
Autopsy
Macrophages
Nucleocapsid protein
Proteostasis
Unfolded protein response
Journal
Cell stress & chaperones
ISSN: 1466-1268
Titre abrégé: Cell Stress Chaperones
Pays: Netherlands
ID NLM: 9610925
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
25
06
2021
accepted:
03
08
2021
revised:
02
08
2021
pubmed:
13
8
2021
medline:
14
10
2021
entrez:
12
8
2021
Statut:
ppublish
Résumé
Vaccinations are widely credited with reducing death rates from COVID-19, but the underlying host-viral mechanisms/interactions for morbidity and mortality of SARS-CoV-2 infection remain poorly understood. Acute respiratory distress syndrome (ARDS) describes the severe lung injury, which is pathologically associated with alveolar damage, inflammation, non-cardiogenic edema, and hyaline membrane formation. Because proteostatic pathways play central roles in cellular protection, immune modulation, protein degradation, and tissue repair, we examined the pathological features for the unfolded protein response (UPR) using the surrogate biomarker glucose-regulated protein 78 (GRP78) and co-receptor for SARS-CoV-2. At autopsy, immunostaining of COVID-19 lungs showed highly elevated expression of GRP78 in both pneumocytes and macrophages compared with that of non-COVID control lungs. GRP78 expression was detected in both SARS-CoV-2-infected and un-infected pneumocytes as determined by multiplexed immunostaining for nucleocapsid protein. In macrophages, immunohistochemical staining for GRP78 from deceased COVID-19 patients was increased but overlapped with GRP78 expression taken from surgical resections of non-COVID-19 controls. In contrast, the robust in situ GRP78 immunostaining of pneumocytes from COVID-19 autopsies exhibited no overlap and was independent of age, race/ethnicity, and gender compared with that from non-COVID-19 controls. Our findings bring new insights for stress-response pathways involving the proteostatic network implicated for host resilience and suggest that targeting of GRP78 expression with existing therapeutics might afford an alternative therapeutic strategy to modulate host-viral interactions during SARS-CoV-2 infections.
Identifiants
pubmed: 34382151
doi: 10.1007/s12192-021-01230-4
pii: 10.1007/s12192-021-01230-4
pmc: PMC8357488
doi:
Substances chimiques
Endoplasmic Reticulum Chaperone BiP
0
HSPA5 protein, human
0
Heat-Shock Proteins
0
Receptors, Coronavirus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
859-868Subventions
Organisme : BLRD VA
ID : I01 BX003833
Pays : United States
Organisme : va merit review
ID : BX003833
Informations de copyright
© 2021. Cell Stress Society International.
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