Host factor PRPF31 is involved in cccDNA production in HBV-replicating cells

Kinoshita, Wataru; Ogura, Naoto; Watashi, Koichi; Wakita, Takaji

doi:10.1016/j.bbrc.2016.11.085

Cited by 16 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, which step(s) POLK and possibly POLH and POLL exactly perform in cccDNA formation remains to be determined. The latest addition, also found via an RNAi screen, is pre-mRNA processing factor 31 (PRPF31; [168]. As PRPF31 is normally involved in splicing, further data will be required to assess how this factor could enhance cccDNA formation.…”

Section: Evidence For a Connection Between Hbv And The Host Dna Damentioning

confidence: 99%

A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond?

Schreiner

Nassal

2017

Viruses

View full text Add to dashboard Cite

Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of a pregenomic (pg) RNA, yielding an unusually structured, viral polymerase-linked relaxed-circular (RC) DNA as genome in infectious particles. Upon infection, RC-DNA is converted into nuclear covalently closed circular (ccc) DNA. Associating with cellular proteins into an episomal minichromosome, cccDNA acts as template for new viral RNAs, ensuring formation of progeny virions. Hence, cccDNA represents the viral persistence reservoir that is not directly targeted by current anti-HBV therapeutics. Eliminating cccDNA will thus be at the heart of a cure for chronic hepatitis B. The low production of HBV cccDNA in most experimental models and the associated problems in reliable cccDNA quantitation have long hampered a deeper understanding of cccDNA molecular biology. Recent advancements including cccDNA-dependent cell culture systems have begun to identify select host DNA repair enzymes that HBV usurps for RC-DNA to cccDNA conversion. While this list is bound to grow, it may represent just one facet of a broader interaction with the cellular DNA damage response (DDR), a network of pathways that sense and repair aberrant DNA structures and in the process profoundly affect the cell cycle, up to inducing cell death if repair fails. Given the divergent interactions between other viruses and the DDR it will be intriguing to see how HBV copes with this multipronged host system.

show abstract

Section: Evidence For a Connection Between Hbv And The Host Dna Damentioning

confidence: 99%

A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond?

Schreiner

Nassal

2017

Viruses

View full text Add to dashboard Cite

show abstract

“…RNAi-mediated gene silencing of tyrosyl-DNA-phosphodiesterase 2, a DNA repair enzyme thought to mediate polymerase release from the relaxed circular DNA, delays its conversion to cccDNA in HepG2 cells [ 31 ]. A recent study has also demonstrated that silencing the expression of pre-mRNA processing factor 31, an HBx-interacting partner, reduces cccDNA levels in HepAD38 cells [ 32 ].…”

Section: Hepatitis B Virus Therapies Under Developmentmentioning

confidence: 99%

Gene Therapy for Chronic HBV—Can We Eliminate cccDNA?

Bloom

Maepa

Ely

et al. 2018

Genes

View full text Add to dashboard Cite

Chronic infection with the hepatitis B virus (HBV) is a global health concern and accounts for approximately 1 million deaths annually. Amongst other limitations of current anti-HBV treatment, failure to eliminate the viral covalently closed circular DNA (cccDNA) and emergence of resistance remain the most worrisome. Viral rebound from latent episomal cccDNA reservoirs occurs following cessation of therapy, patient non-compliance, or the development of escape mutants. Simultaneous viral co-infections, such as by HIV-1, further complicate therapeutic interventions. These challenges have prompted development of novel targeted hepatitis B therapies. Given the ease with which highly specific and potent nucleic acid therapeutics can be rationally designed, gene therapy has generated interest for antiviral application. Gene therapy strategies developed for HBV include gene silencing by harnessing RNA interference, transcriptional inhibition through epigenetic modification of target DNA, genome editing by designer nucleases, and immune modulation with cytokines. DNA-binding domains and effectors based on the zinc finger (ZF), transcription activator-like effector (TALE), and clustered regularly interspaced short palindromic repeat (CRISPR) systems are remarkably well suited to targeting episomal cccDNA. This review discusses recent developments and challenges facing the field of anti-HBV gene therapy, its potential curative significance and the progress towards clinical application.

show abstract

“…. 也有研究发现, PRPF31 (pre-mRNA processing factors 31)通过与HBX相互作用促进了cccDNA的形成, 但是PRPF31主要在RNA剪切过程中发挥作用, 其具体对cccDNA的影响尚未明确 [19] . 除了DNA损伤修复机制外, 许多宿主DNA聚合酶的作用对cccDNA形成也是至关重要.…”

Section: 当Hbv感染宿主细胞时其包膜表面L蛋白n端unclassified

Host factors involved in HBV cccDNA formation and transcription

He¹,

Shi²

2019

Chin. Sci. Bull.

View full text Add to dashboard Cite

Host factor PRPF31 is involved in cccDNA production in HBV-replicating cells

Cited by 16 publications

References 36 publications

A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond?

A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond?

Gene Therapy for Chronic HBV—Can We Eliminate cccDNA?

Host factors involved in HBV cccDNA formation and transcription

Contact Info

Product

Resources

About