Host RNA quality control as a hepatitis B antiviral target.

Host RNA quality control as a hepatitis B antiviral target. Antiviral Res. 2020 Nov 23;:104972 Authors: Block TM, Young JAT, Javanbakht H, Sofia MJ, Zhou T Abstract Inhibition of the host RNA polyadenylating polymerases, PAPD5 and PAPD7 (PAPD5/7), with dihydroxyquinoline (DHQ), a small orally available, molecule, results in a rapid and selective degradation of hepatitis B virus (HBV) RNA, and hence reduction in the amounts of viral gene products. DHQ, is a first in class investigational agent and could represent an entirely new category of HBV antivirals. PAPD5 and PAPD7 are non-canonical, cell specified, polyadenylating polymerases, also called terminal nucleotidyl transferases 4B and 4A (TENT4B/A), respectively. They are involved in the degradation of poor-quality cell transcripts, mostly non-coding RNAs and in the maturation of a sub-set of transcripts. They also appear to play a role in shielding some mRNA from degradation. The results of studies with DHQ, along with other recent findings, provide evidence that repression of the PAPD5/7 arm of the cell "RNA quality control" pathway, causes a profound (multi-fold) reduction rather than increase, in the amount of HBV pre-genomic, pre-core and HBsAg mRNA levels in tissue culture and animal models, as well. In this review we will briefly discuss the need for new HBV therapeutics and provide background about HBV transcription. We also discuss cellular degradation of host transcripts, ...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research