Abstract
Enveloped viruses pose constant threat to hosts from ocean to land. Virion particle release from cell surface is a critical step in the viral life cycle for most enveloped viruses, making it a common antiviral target for the host defense system. Here we report that host factor TMEM106A inhibits the release of enveloped viruses from the cell surface. TMEM106A is a type II transmembrane protein localized on the plasma membrane and can be incorporated into HIV-1 virion particles. Through intermolecular interactions of its C-terminal domains on virion particle and plasma membrane, TMEM106A traps virion particles to the cell surface. HIV-1 Env interacts with TMEM106A to interfere with the intermolecular interactions and partially suppresses its antiviral activity. TMEM106A orthologs from various species displayed potent antiviral activity against multiple enveloped viruses. These results suggest that TMEM106A is an evolutionarily conserved antiviral factor that inhibits the release of enveloped viruses from the cell surface.