Promyelocytic leukemia (PML) suppresses hepatitis B virus cccDNA transcription through SUMOylation- and SMC5/6-dependent mechanisms
Wu, J.; Li, F.; Ahodantin, J.; Funaki, M.; Su, L.
Show abstract
Chronic hepatitis B virus (HBV) infection persists under current antiviral therapy because covalently closed circular DNA (cccDNA) remains in the infected hepatocytes as a durable transcriptional template. Although type I interferon (IFN-I) can reduce HBV cccDNA gene expression, the host effectors and mechanisms that restrict cccDNA remain incompletely defined. Using a minicircle-based HBV cccDNA expressing a Gaussia luciferase reporter gene (mcHBV-GLuc), we investigated how promyelocytic leukemia protein (PML) suppresses HBV cccDNA activity. Multiple PML isoforms reduced cccDNA-driven reporter activity and HBsAg production, and HBx-deficient ({Delta}X) mcHBV cccDNA was more susceptible than wild-type cccDNA to PML-mediated inhibition. Interestingly, efficient antiviral activity required the major PML SUMOylation sites. Disruption of SMC5/6 function attenuated PML-mediated repression of HBx-deficient cccDNA, associated with reduced PML SUMOylation and PML nuclear-body organization. These findings identify PML as a SUMO-dependent inhibitor of HBV cccDNA activity and reveal a context-dependent functional relationship between PML and SMC5/6 that is modulated by HBx.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The kinesin KIF4 mediates HBV/HDV entry through regulation of surface NTCP localization and can be targeted by RXR agonists in vitro. 93%
- Cooperativity between the 3’ untranslated region microRNA binding sites is critical for the virulence of eastern equine encephalitis virus 93%
- Separate domains of G3BP promote efficient clustering of alphavirus replication complexes and recruitment of the translation initiation machinery 92%
Similar papers in this journal
- Host poly(A) polymerases PAPD5 and PAPD7 provide two layers of protection that ensure the integrity and stability of hepatitis B virus RNA 95%
- Hepatitis C virus infection is inhibited by a non-canonical antiviral signaling pathway targeted by NS3-NS4A 95%
- VAMP8 contributes to TRIM6-mediated type-I interferon antiviral response during West Nile virus infection 93%
Similar papers in this journal
- HCMV promotes viral reactivation through the coordinated regulation of Notch signaling by UL8 and miR-UL36 92%
- Interferon-Induced Transmembrane Proteins Inhibit Infection by the Kaposis Sarcoma-Associated Herpesvirus and the Related Rhesus Monkey Rhadinovirus in a Cell Type-Specific Manner. 92%
- Extensive epitranscriptomic methylation of A and C residues on murine leukemia virus transcripts enhances viral gene expression 92%
Similar papers in this journal
- Attenuation of IFITM proteins antiviral activity through sequestration into intraluminal vesicles of late endosomes 92%
- Conserved induction of distinct antiviral signalling kinetics by primate interferon lambda 4 proteins 91%
- Stable characteristics of intrapopulation heterogeneity in virus-specific Th1 cells during chronic viral challenge infection 90%
Similar papers in this journal
- Structural features stabilized by divalent cation coordination within hepatitis E virus ORF1 are critical for viral replication 92%
- A CRISPR-based instant DNA repositioning system and the early intranuclear life of HSV-1 92%
- Human liver organoids; a patient-derived primary model for HBV Infection and Related Hepatocellular Carcinoma 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.