MARCH8 Ubiquitinates the Hepatitis C Virus Nonstructural 2 Protein and Mediates Viral Envelopment

Abstract : Graphical Abstract Highlights d Ubiquitin signaling factors interact with NS2 and play a role in HCV infection d MARCH8 mediates K63-linked ubiquitination of HCV NS2 and ESCRT recruitment d MARCH8 is required for Flaviviridae infection and intracellular envelopment of HCV d MARCH8 is a potential target for host-targeted antiviral strategies In Brief The mechanisms that regulate intracellular viral envelopment are unknown. Kumar et al. report that MARCH8 catalyzes K63-linked polyubiquitination of the HCV nonstructural 2 protein and subsequently ESCRT recruitment and HCV envelopment. MARCH8 is required for infection with other Flaviviridae family members, thereby representing a potential host target for antiviral strategies.