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Journal article
Development of a novel system to study hepatitis delta virus genome replication
Journal of virology, v 79(13), pp 8182-8188
01 Jul 2005
PMCID: PMC1143748
PMID: 15956563
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hepatitis delta virus (HDV) genome replication requires the virus-encoded small delta protein (deltaAg). During replication, nucleotide sequence changes accumulate on the HDV RNA, leading to the translation of deltaAg species that are nonfunctional or even inhibitory. A replication system was devised where all deltaAg was conditionally provided from a separate and unchanging source. A line of human embryonic kidney cells was stably transfected with a single copy of cDNA encoding small deltaAg, with expression under tetracycline (TET) control. Next, HDV genome replication was initiated in these cells by transfection with a mutated RNA unable to express deltaAg. Thus, replication of this RNA was under control of the TET-inducible deltaAg. In the absence of TET, there was sufficient deltaAg to allow a low level of HDV replication that could be maintained for at least 1 year. When TET was added, both deltaAg and genomic RNA increased dramatically within 2 days. With clones of such cells, designated 293-HDV, the burst of HDV RNA replication interfered with cell cycling. Within 2 days, there was a fivefold enhancement of G1/G0 cells relative to both S and G2/M cells, and by 6 days, there was extensive cell detachment and death. These findings and those of other studies that are under way demonstrate the potential applications of this experimental system.
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Details
- Title
- Development of a novel system to study hepatitis delta virus genome replication
- Creators
- Jinhong Chang - Fox Chase Cancer CenterSeverin O GudimaChi TarnXingcao NieJohn M Taylor
- Publication Details
- Journal of virology, v 79(13), pp 8182-8188
- Publisher
- American Society for Microbiology (ASM)
- Grant note
- R01 AI026522 / NIAID NIH HHS P30 CA006927 / NCI NIH HHS CA-06927 / NCI NIH HHS AI-26522 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000229866700023
- Scopus ID
- 2-s2.0-20744460577
- Other Identifier
- 991020547451304721
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- Web of Science research areas
- Virology