Timothy Ting-Hsuan Wu, Kyle J Travaglini, Arjun Rustagi, Duo Xu, Yue Zhang, Leonid Andronov, SoRi Jang, Astrid Gillich, Roozbeh Dehghannasiri, Giovanny J Martínez-Colón, Aimee Beck, Daniel Dan Liu, Aaron J Wilk, Maurizio Morri, Winston L Trope, Rob Bierman, Irving L Weissman, Joseph B Shrager, Stephen R Quake, Christin S Kuo, Julia Salzman, W E Moerner, Peter S Kim, Catherine A Blish, Mark A Krasnow
Early stages of deadly respiratory diseases including COVID-19 are challenging to elucidate in humans. Here, we define cellular tropism and transcriptomic effects of SARS-CoV-2 virus by productively infecting healthy human lung tissue and using scRNA-seq to reconstruct the transcriptional program in "infection pseudotime" for individual lung cell types. SARS-CoV-2 predominantly infected activated interstitial macrophages (IMs), which can accumulate thousands of viral RNA molecules, taking over 60% of the cell transcriptome and forming dense viral RNA bodies while inducing host profibrotic (TGFB1, SPP1) and inflammatory (early interferon response, CCL2/7/8/13, CXCL10, and IL6/10) programs and destroying host cell architecture...
June 3, 2024: Journal of Experimental Medicine