Control of APOBEC3B induction and cccDNA decay by NF-κB and miR-138-5p

Abstract

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Alpha‐kinase 1 (ALPK1) agonist DF‐006 demonstrates potent efficacy in mouse and primary human hepatocyte (PHH) models of hepatitis B

“…These effectors exert anti-HBV function through interfering with HBV reverse transcription and replication, prompting cccDNA for degradation, or reducing replenishment of cccDNA pool. [28][29][30][31] In addition, we found that DF-006 upregulated toll-like receptor pathway genes including Tlr2 and Tlr3, activation of which has been shown to suppress HBV replication. [32] Of note, we found that induction of NF-κB-induced genes occurred in isolated hepatocytes as well as liver tissue.…”

“…In assessing interferon‐stimulated genes (ISG)27 that are mediated indirectly or directly by NF‐κB and have anti‐HBV activity, we noted upregulation of Ddx58 (RNA sensor RIG‐I [ RIG‐I ]), Apobec3 , Isg20 , and Trex1 . These effectors exert anti‐HBV function through interfering with HBV reverse transcription and replication, prompting cccDNA for degradation, or reducing replenishment of cccDNA pool 28–31. In addition, we found that DF‐006 upregulated toll‐like receptor pathway genes including Tlr2 and Tlr3 , activation of which has been shown to suppress HBV replication 32…”

Signaling Induced by Chronic Viral Hepatitis: Dependence and Consequences

“…Signaling pathways are established targets in cancer therapy [ 177 ] and have previously drawn attention as targets for cancer prevention attenuating liver disease progression [ 178 , 179 ]. Host signaling-targeting approaches to battle chronic infection have been discussed [ 133 , 180 , 181 ] as they hold the potential to lower the genetic barrier of resistance to direct-acting antivirals. However, currently, only interferons are in clinical use targeting chronic viral hepatitis.…”

Receptor Specificity Engineering of TNF Superfamily Ligands

“…In addition, LTβR agonist 31G4D8 (antibody) and LIGHT-R228E mutein induces ROS production, resulting in cancer cell apoptosis [155]. Recently, it was shown that LTβR agonistic antibody BS1 initiates apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) expression through noncanonical NFκB signaling to suppress hepatitis B virus (HBV) replication [159][160][161].…”