Respiratory viral infections prime accelerated lung cancer growth [scATAC-Seq]

The COVID-19 pandemic has highlighted long-term health consequences of viral pneumonia, yet its potential impact on cancer development and growth remains poorly understood. Here, we show that prior SARS-CoV-2 or influenza infection accelerates lung tumor progression by reprogramming the local immune landscape. To test whether heightened cytokine responses after tumor initiation reflect durable epigenetic priming, we performed scATAC-seq on total lung cells from SARS-CoV-2–infected mice (28 d.p.i.) and PBS controls. Across macrophages, epithelial cells, fibroblasts, and endothelial cells, infection induced mild-to-moderate increases in chromatin accessibility at the Csf3 promoter and putative enhancers, with similar accessibility gains at Il6, Il1b, Cxcl1, and Cxcl5 loci in multiple compartments. Motif enrichment and regulon analyses further indicated increased accessibility/activity of NF-?B and AP-1, along with elevated STAT3/STAT4 activity. Collectively, these data demonstrate that prior respiratory viral infection drives long-lasting epigenetic remodeling of cytokine loci in lung immune and structural cells. Overall design: Lung single-cell suspensions freshly isolated from PBS- or SCV2-infected mice at 28 d.p.i. were processed for ATAC library construction using the Chromium Next GEM Single Cell ATAC Kit v2 (10x Genomics), following the manufacturer's protocol.