{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328992/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328992"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Beyond ACE2: DPP4 Engagement Redefines SARS-CoV-2 Receptor Tropism","description":"The continued evolution of SARS-CoV-2 has produced variants with enhanced transmissibility despite reduced binding affinity to the canonical entry receptor ACE2, suggesting the involvement of additional host factors. Here, we integrate large-scale sequence analysis, structure-informed machine learning, biochemical assays, cell-based entry models, and in vivo infection studies to examine receptor usage diversification in recent SARS-CoV-2 variants. We find that multiple post-Omicron lineages, including XBB-derived variants, exhibit increased functional engagement of dipeptidyl peptidase 4 (DPP4), accompanied by reduced reliance on ACE2-mediated entry in defined experimental contexts. In human DPP4 knock-in mice, representative XBB variants display enhanced replication with limited pulmonary pathology. Together, these findings support a model in which SARS-CoV-2 evolution is characterized by diversification of receptor engagement strategies, highlighting DPP4 as a functionally relevant entry factor that may contribute to viral fitness under immune pressure.","dates":{"publication":"2026/04/28"},"accession":"GSE328992","cross_references":{"GSM":["GSM9695479","GSM9695476","GSM9695487","GSM9695475","GSM9695486","GSM9695489","GSM9695478","GSM9695488","GSM9695477","GSM9695472","GSM9695483","GSM9695482","GSM9695471","GSM9695485","GSM9695474","GSM9695473","GSM9695484","GSM9695490","GSM9695481","GSM9695491","GSM9695480"],"GPL":["24247"],"GSE":["328992"],"taxon":["Mus musculus"]}}