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

Sathish Kumar (1) , Rina Barouch-Bentov (1) , Fei Xiao (1) , Stanford Schor (1) , Szuyuan Pu (1) , Elise Biquand (2) , Albert Lu (1) , Brett Lindenbach (3) , Yves Jacob (2) , Caroline Demeret (2) , Shirit Einav (1)

1 Stanford School of Medicine [Stanford]
2 GMV-ARN (UMR_3569 / U-Pasteur_2) - Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses
3 YSM - Yale School of Medicine [New Haven, Connecticut]

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.

Keywords: ESCRT; HCV; assembly; MARCH8; envelopment; hepatitis C virus; intracellular membrane trafficking; proteomics; ubiquitination; virus-host interactions

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Virology

Sathish Kumar, Rina Barouch-Bentov, Fei Xiao, Stanford Schor, Szuyuan Pu, et al.. MARCH8 Ubiquitinates the Hepatitis C Virus Nonstructural 2 Protein and Mediates Viral Envelopment. Cell Reports, 2019, 26 (7), pp.1800-1814.e5. ⟨10.1016/j.celrep.2019.01.075⟩. ⟨pasteur-02077482⟩