Evidence of SARS-CoV-2 infection in postmortem lung, kidney, and liver samples, revealing cellular targets involved in COVID-19 pathogenesis.
Viviana Falcón-CamaTeresita Montero GonzálezEmilio F Acosta-MedinaGerardo Guillen-NietoJorge Berlanga-AcostaCelia Fernández-OrtegaAnabel Alfonso-FalcónNathalie Gilva-RodríguezLilianne López-NocedoDaina Cremata-GarcíaMariuska Matos-TerreroGiselle Pentón-RolIris ValdésLeonardo Oramas-DíazAnamarys Suarez-BatistaEnrique Noa-RomeroOtto Cruz-SuiDaisy SánchezAmanda I Borrego-DíazJuan E Valdés-CarrerasAnanayla VizcainoJosé Suárez-AlbaRodolfo Valdés-VélizGretchen BergadoMiguel A GonzálezTays HernandezRydell Alvarez-ArzolaAnna C Ramírez-SuárezDionne Casillas-CasanovaGilda Lemos-PérezOmar R Blanco-ÁguilaAngelina DíazYorexis GonzálezMónica Bequet-RomeroJavier Marín-PridaJulio C Hernández-PereraLeticia Del Rosario-CruzAlina P Marin-DíazMaritza González-BravoIsrael BorrajeroNelson Acosta-RiveroPublished in: Archives of virology (2023)
There is an urgent need to understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-host interactions involved in virus spread and pathogenesis, which might contribute to the identification of new therapeutic targets. In this study, we investigated the presence of SARS-CoV-2 in postmortem lung, kidney, and liver samples of patients who died with coronavirus disease (COVID-19) and its relationship with host factors involved in virus spread and pathogenesis, using microscopy-based methods. The cases analyzed showed advanced stages of diffuse acute alveolar damage and fibrosis. We identified the SARS-CoV-2 nucleocapsid (NC) in a variety of cells, colocalizing with mitochondrial proteins, lipid droplets (LDs), and key host proteins that have been implicated in inflammation, tissue repair, and the SARS-CoV-2 life cycle (vimentin, NLRP3, fibronectin, LC3B, DDX3X, and PPARγ), pointing to vimentin and LDs as platforms involved not only in the viral life cycle but also in inflammation and pathogenesis. SARS-CoV-2 isolated from a patient´s nasal swab was grown in cell culture and used to infect hamsters. Target cells identified in human tissue samples included lung epithelial and endothelial cells; lipogenic fibroblast-like cells (FLCs) showing features of lipofibroblasts such as activated PPARγ signaling and LDs; lung FLCs expressing fibronectin and vimentin and macrophages, both with evidence of NLRP3- and IL1β-induced responses; regulatory cells expressing immune-checkpoint proteins involved in lung repair responses and contributing to inflammatory responses in the lung; CD34 + liver endothelial cells and hepatocytes expressing vimentin; renal interstitial cells; and the juxtaglomerular apparatus. This suggests that SARS-CoV-2 may directly interfere with critical lung, renal, and liver functions involved in COVID-19-pathogenesis.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- coronavirus disease
- endothelial cells
- induced apoptosis
- oxidative stress
- cell cycle arrest
- life cycle
- high glucose
- signaling pathway
- insulin resistance
- diabetic rats
- high resolution
- single molecule
- vascular endothelial growth factor
- hepatitis b virus
- nlrp inflammasome
- optical coherence tomography
- skeletal muscle
- metabolic syndrome
- simultaneous determination
- case report
- liver injury