APOBEC3B Promotes SARS-CoV-2 Through Activation of PKR and eIF2-alpha and AMPD2 Dysregulation

APOBEC3B has been implicated in host-virus interactions, but its role in SARS-CoV-2 infection is unclear. To further investigate A3B's role in severe COVID-19, we employed Geneformer, a transformer-based machine learning model, which predicted that A3B knockout would perturb AMPD2, a key enzyme in purine metabolism and immune regulation. We validated this prediction using bulk RNA-seq and clinical scRNA-seq data, confirming that AMPD2 expression is downregulated in severe COVID-19 but restored upon A3B knockdown. Together, these findings suggest that A3B plays a proviral role in SARS-CoV-2 infection by modulating translational control and immune regulatory networks, warranting further studies to elucidate the underlying mechanistic details.