Potent inhibition of human Hepatitis B virus replication by a host factor Vps4

Vps4 is a host factor known to be involved in cellular vacuolar protein sorting. We report here that HBV replication and secretion can be significantly inhibited by Vps4 dominant negative, ATPase-defective, mutants K173Q and E228Q. In contrast, wild-type Vps4 at low dose can inhibit HBV replication more effectively in human hepatoblastoma cell line HepG2, than in human hepatoma cell line Huh7. To our knowledge, this is the first demonstration of an anti-HBV potential of dominant negative mutants of a protein sorting host factor Vps4.