Jin Wei, Mia Madel Alfajaro, Wesley L Cai, Vincent R Graziano, Madison S Strine, Renata B Filler, Scott B Biering, Sylvia A Sarnik, Sonam Patel, Bridget L Menasche, Susan R Compton, Silvana Konermann, Patrick D Hsu, Robert C Orchard, Qin Yan, Craig B Wilen
Identification of host determinants of coronavirus infection informs mechanisms of pathogenesis and may provide novel therapeutic targets. Here, we demonstrate that the histone demethylase KDM6A promotes infection of diverse coronaviruses, including SARS-CoV, SARS-CoV-2, MERS-CoV and mouse hepatitis virus (MHV) in a demethylase activity-independent manner. Mechanistic studies reveal that KDM6A promotes viral entry by regulating expression of multiple coronavirus receptors, including ACE2, DPP4 and Ceacam1. Importantly, the TPR domain of KDM6A is required for recruitment of the histone methyltransferase KMT2D and histone deacetylase p300...
July 2023: PLoS Pathogens