S-Palmitoylation and Sterol Interactions Mediate Antiviral Specificity of IFITMs

• DOI: 10.1021/acschembio.2c00176
• Publication Date: 2022-07-21T14:14:46Z
• Authors: Tandrila Das; Xinglin Yang; Hwayoung Lee; Emma H. Garst; Estefania Valencia; Kartik Chandran; Wonpil Im; Howard C. Hang
• Keywords: Palmitoylation

Interferon-induced transmembrane proteins (IFITM1, 2, and 3) are important antiviral that active against many viruses, including influenza A virus (IAV), dengue (DENV), Ebola (EBOV), Zika (ZIKV), severe acute respiratory syndrome coronavirus (SARS-CoV). IFITM exhibit specificity in activity, but their distinct mechanisms of action regulation unclear. Since S-palmitoylation cholesterol homeostasis crucial for viral infections, we investigated interactions with by photoaffinity cross-linking mammalian cells along molecular dynamic simulations nuclear magnetic resonance analysis vitro. These studies suggest can directly interact S-palmitoylated IFITMs alter the conformation membrane bilayers. Notably, discovered levels regulate differential protein activity toward IAV, SARS-CoV-2, EBOV. Our modulation interaction influence host susceptibility to different viruses.