tetano
Editor, Senior Moderator
Arch Virol
. 2023 Feb 26;168(3):96.
doi: 10.1007/s00705-023-05711-y.
Evidence of SARS-CoV-2 infection in postmortem lung, kidney, and liver samples, revealing cellular targets involved in COVID-19 pathogenesis
Viviana Falcón-Cama[SUP] #[/SUP][SUP] 1 2 [/SUP], Teresita Montero-González[SUP] #[/SUP][SUP] 3 [/SUP], Emilio F Acosta-Medina[SUP] 4 5 [/SUP], Gerardo Guillen-Nieto[SUP] 6 7 [/SUP], Jorge Berlanga-Acosta[SUP] 6 7 [/SUP], Celia Fernández-Ortega[SUP] 6 7 [/SUP], Anabel Alfonso-Falcón[SUP] 8 [/SUP], Nathalie Gilva-Rodríguez[SUP] 6 [/SUP], Lilianne López-Nocedo[SUP] 6 [/SUP], Daina Cremata-García[SUP] 6 [/SUP], Mariuska Matos-Terrero[SUP] 6 [/SUP], Giselle Pentón-Rol[SUP] 6 7 [/SUP], Iris Valdés[SUP] 6 [/SUP], Leonardo Oramas-Díaz[SUP] 6 [/SUP], Anamarys Suarez-Batista[SUP] 9 [/SUP], Enrique Noa-Romero[SUP] 9 [/SUP], Otto Cruz-Sui[SUP] 9 [/SUP], Daisy Sánchez[SUP] 10 [/SUP], Amanda I Borrego-Díaz[SUP] 10 [/SUP], Juan E Valdés-Carreras[SUP] 10 [/SUP], Ananayla Vizcaino[SUP] 10 [/SUP], José Suárez-Alba[SUP] 6 [/SUP], Rodolfo Valdés-Véliz[SUP] 6 [/SUP], Gretchen Bergado[SUP] 11 [/SUP], Miguel A González[SUP] 11 [/SUP], Tays Hernandez[SUP] 11 [/SUP], Rydell Alvarez-Arzola[SUP] 11 [/SUP], Anna C Ramírez-Suárez[SUP] 6 [/SUP], Dionne Casillas-Casanova[SUP] 6 [/SUP], Gilda Lemos-Pérez[SUP] 6 [/SUP], Omar R Blanco-Águila[SUP] 12 [/SUP], Angelina Díaz[SUP] 10 [/SUP], Yorexis González[SUP] 10 [/SUP], Mónica Bequet-Romero[SUP] 6 [/SUP], Javier Marín-Prida[SUP] 13 [/SUP], Julio C Hernández-Perera[SUP] 8 [/SUP], Leticia Del Rosario-Cruz[SUP] 14 [/SUP], Alina P Marin-Díaz[SUP] 15 [/SUP], Maritza González-Bravo[SUP] 7 [/SUP], Israel Borrajero[SUP] 16 [/SUP], Nelson Acosta-Rivero[SUP] #[/SUP][SUP] 17 18 [/SUP]
Affiliations
Abstract
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[SUP]+[/SUP] 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.
. 2023 Feb 26;168(3):96.
doi: 10.1007/s00705-023-05711-y.
Evidence of SARS-CoV-2 infection in postmortem lung, kidney, and liver samples, revealing cellular targets involved in COVID-19 pathogenesis
Viviana Falcón-Cama[SUP] #[/SUP][SUP] 1 2 [/SUP], Teresita Montero-González[SUP] #[/SUP][SUP] 3 [/SUP], Emilio F Acosta-Medina[SUP] 4 5 [/SUP], Gerardo Guillen-Nieto[SUP] 6 7 [/SUP], Jorge Berlanga-Acosta[SUP] 6 7 [/SUP], Celia Fernández-Ortega[SUP] 6 7 [/SUP], Anabel Alfonso-Falcón[SUP] 8 [/SUP], Nathalie Gilva-Rodríguez[SUP] 6 [/SUP], Lilianne López-Nocedo[SUP] 6 [/SUP], Daina Cremata-García[SUP] 6 [/SUP], Mariuska Matos-Terrero[SUP] 6 [/SUP], Giselle Pentón-Rol[SUP] 6 7 [/SUP], Iris Valdés[SUP] 6 [/SUP], Leonardo Oramas-Díaz[SUP] 6 [/SUP], Anamarys Suarez-Batista[SUP] 9 [/SUP], Enrique Noa-Romero[SUP] 9 [/SUP], Otto Cruz-Sui[SUP] 9 [/SUP], Daisy Sánchez[SUP] 10 [/SUP], Amanda I Borrego-Díaz[SUP] 10 [/SUP], Juan E Valdés-Carreras[SUP] 10 [/SUP], Ananayla Vizcaino[SUP] 10 [/SUP], José Suárez-Alba[SUP] 6 [/SUP], Rodolfo Valdés-Véliz[SUP] 6 [/SUP], Gretchen Bergado[SUP] 11 [/SUP], Miguel A González[SUP] 11 [/SUP], Tays Hernandez[SUP] 11 [/SUP], Rydell Alvarez-Arzola[SUP] 11 [/SUP], Anna C Ramírez-Suárez[SUP] 6 [/SUP], Dionne Casillas-Casanova[SUP] 6 [/SUP], Gilda Lemos-Pérez[SUP] 6 [/SUP], Omar R Blanco-Águila[SUP] 12 [/SUP], Angelina Díaz[SUP] 10 [/SUP], Yorexis González[SUP] 10 [/SUP], Mónica Bequet-Romero[SUP] 6 [/SUP], Javier Marín-Prida[SUP] 13 [/SUP], Julio C Hernández-Perera[SUP] 8 [/SUP], Leticia Del Rosario-Cruz[SUP] 14 [/SUP], Alina P Marin-Díaz[SUP] 15 [/SUP], Maritza González-Bravo[SUP] 7 [/SUP], Israel Borrajero[SUP] 16 [/SUP], Nelson Acosta-Rivero[SUP] #[/SUP][SUP] 17 18 [/SUP]
Affiliations
- PMID: 36842152
- DOI: 10.1007/s00705-023-05711-y
Abstract
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[SUP]+[/SUP] 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.