The E3 ubiquitin ligase MARCHF8 restricts HSV-1 infection by inhibiting replication of the viral genome

Abstract

Host cell restriction factors are intracellular proteins that target and inhibit virus replication. Membrane-associated RING-CH finger (MARCHF) proteins are a family of intracellular E3-ubiquitin ligases and some, including MARCHF8, have been implicated in restricting the replication of diverse RNA viruses. However, little is currently known as to whether MARCHF proteins mediate antiviral activity against DNA viruses. Herein, we used a doxycycline-inducible overexpression system to demonstrate that human MARCHF1 and MARCHF8 potently restrict productive HSV-1 replication and assessed MARCHF8-mediated restriction of HSV-1 in detail. A functional RING-CH domain and a tyrosine-based motif, locat..