Efficient pyrophosphorolysis by a hepatitis B virus polymerase may be a primer-unblocking mechanism

Proceedings of the National Academy of Sciences of the United States of America
S UrbanD L Tyrrell

Abstract

Effective antiviral agents are thought to inhibit hepatitis B virus (HBV) DNA synthesis irreversibly by chain termination because reverse transcriptases (RT) lack an exonucleolytic activity that can remove incorporated nucleotides. However, since the parameters governing this inhibition are poorly defined, fully delineating the catalytic mechanism of the HBV-RT promises to facilitate the development of antiviral drugs for treating chronic HBV infection. To this end, pyrophosphorolysis and pyrophosphate exchange, two nonhydrolytic RT activities that result in the removal of newly incorporated nucleotides, were characterized by using endogenous avian HBV replication complexes assembled in vivo. Although these activities are presumed to be physiologically irrelevant for every polymerase examined, the efficiency with which they are catalyzed by the avian HBV-RT strongly suggests that it is the first known polymerase to catalyze these reactions under replicative conditions. The ability to remove newly incorporated nucleotides during replication has important biological and clinical implications: these activities may serve a primer-unblocking function in vivo. Analysis of pyrophosphorolysis on chain-terminated DNA revealed that the p...Continue Reading

References

Jun 1, 1989·Virology·R Girones, R H Miller
Nov 13, 1986·Biochimica Et Biophysica Acta·Z G ChidgeavadzeM K Kukhanova
Jan 1, 1986·Intervirology·I D GustA J Zuckerman
May 11, 1995·Biochemical Pharmacology·T E Kitos, D L Tyrrell
Jan 1, 1996·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A Y HoweD L Tyrrell
Jan 1, 1996·Methods in Enzymology·J Hu, C Seeger
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·A ZlotnickP T Wingfield
Jun 10, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M I AllenL D Condreay
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·P R MeyerW A Scott
Nov 26, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·X XiongC S Gibbs
Apr 9, 1999·Clinical Microbiology Reviews·F J Mahoney
Jul 8, 1999·Molecular Cell·S A WynneA G Leslie
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·S G SarafianosE Arnold

❮ Previous
Next ❯

Citations

Jan 8, 2004·Journal of Hepatology·Stephen Locarnini
Sep 21, 2010·Nature Structural & Molecular Biology·Xiongying TuEddy Arnold
Jul 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Huiling YangShelly Xiong
Jun 22, 2012·Journal of Virology·Joshua T SchifferKeith R Jerome
Aug 2, 2014·Cellular and Molecular Life Sciences : CMLS·Aartjan J W te Velthuis
Sep 10, 2015·Proceedings of the National Academy of Sciences of the United States of America·Lalith PereraSamuel H Wilson
Jun 24, 2003·Reviews in Medical Virology·Ruth Chin, Stephen Locarnini
Jun 28, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Christopher E WestlandUNKNOWN 437 and 438 Study Teams
Aug 2, 2017·Nature Chemical Biology·David D ShockSamuel H Wilson
Jun 1, 2018·Nucleic Acids Research·Jithesh Kottur, Deepak T Nair

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.