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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Characterization of novel hepadnaviral RNA species accumulated in hepatoma cells treated with viral DNA polymerase inhibitors
Antiviral research, v 131, pp 40-48
01 Jul 2016
PMID: 27083116
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Inhibitors of hepadnaviral DNA polymerases are predicted to inhibit both minus and plus strand of viral DNA synthesis and arrest viral DNA replication at the stage of pregenomic (pg) RNA-containing nudeocapsids. However, analyses of the RNA species of human and duck hepatitis B viruses (HBV and DHBV, respectively) in hepatoma cells treated with viral DNA polymerase inhibitors revealed the genesis of novel RNA species migrating slightly faster than the full-length pgRNA. The DNA polymerase inhibitor induced accumulation of these RNA species were abolished in the presence of alpha-interferon or HBV nucleocapsid assembly inhibitors. Moreover, they were protected from microccocal nuclease digestion and devoid of a poly-A tail. These characteristics suggest that the novel RNA species are most likely generated from RNase H cleavage of encapsidated pgRNA, after primer translocation and synthesis of the 5' terminal portion of minus strand DNA. In support of this hypothesis, DNA polymerase inhibitor treatment of chicken hepatoma cells transfected with a DHBV genome encoding an RNase H inactive DNA polymerase (E696H) failed to produce such RNA species. Our results thus suggest that the currently available DNA polymerase inhibitors do not efficiently arrest minus strand DNA synthesis at the early stage in hepatocytes. Hence, development of novel antiviral agents that more potently suppress viral DNA synthesis or viral nucleocapsid assembly inhibitors that are mechanistically complementary to the currently available DNA polymerase inhibitors are warranted. (C) 2016 Published by Elsevier B.V.
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Details
- Title
- Characterization of novel hepadnaviral RNA species accumulated in hepatoma cells treated with viral DNA polymerase inhibitors
- Creators
- Pinghu Zhang - China Pharmaceut Univ, Jiangsu Key Lab New Drug Screening, Nanjing 210009, Peoples R ChinaFei Liu - Baruch S. Blumberg InstituteFang Guo - Baruch S. Blumberg InstituteQiong Zhao - Baruch S. Blumberg InstituteJinhong Chang - Baruch S. Blumberg InstituteJu-Tao Guo - Baruch S. Blumberg Institute
- Publication Details
- Antiviral research, v 131, pp 40-48
- Publisher
- Elsevier
- Number of pages
- 9
- Grant note
- R01 AI113267 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01AI113267 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Jiangsu Overseas research& training program for University Prominent Young & Middle-aged Teachers and Presidents NCET-12-0975 / Program for New Century Excellent Talents in University; Program for New Century Excellent Talents in University (NCET) ZJ11206 / Fundamental Research Funds for the Central Universities Hepatitis B Foundation through an appropriation from the Commonwealth of Pennsylvania
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000378960800006
- Scopus ID
- 2-s2.0-84964253323
- Other Identifier
- 991020547320504721
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- Collaboration types
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy
- Virology