Abstract:
:High rates of genetic variation ensure the survival of RNA viruses. Although this variation is thought to result from error-prone replication, RNA viruses must also maintain highly conserved genomic segments. A balance between conserved and variable viral elements is especially important in order for viruses to avoid "error catastrophe." Ribavirin has been shown to induce error catastrophe in other RNA viruses. We therefore used a novel hepatitis C virus (HCV) replication system to determine relative mutation frequencies in variable and conserved regions of the HCV genome, and we further evaluated these frequencies in response to ribavirin. We sequenced the 5' untranslated region (5' UTR) and the core, E2 HVR-1, NS5A, and NS5B regions of replicating HCV RNA isolated from cells transfected with a T7 polymerase-driven full-length HCV cDNA plasmid containing a cis-acting hepatitis delta virus ribozyme to control 3' cleavage. We found quasispecies in the E2 HVR-1 and NS5B regions of untreated replicating viral RNAs but not in conserved 5' UTR, core, or NS5A regions, demonstrating that important cis elements regulate mutation rates within specific viral segments. Neither T7-driven replication nor sequencing artifacts produced these nucleotide substitutions in control experiments. Ribavirin broadly increased error generation, especially in otherwise invariant regions, indicating that it acts as an HCV RNA mutagen in vivo. Similar results were obtained in hepatocyte-derived cell lines. These results demonstrate the potential utility of our system for the study of intrinsic factors regulating genetic variation in HCV. Our results further suggest that ribavirin acts clinically by promoting nonviable HCV RNA mutation rates. Finally, the latter result suggests that our replication model may be useful for identifying agents capable of driving replicating virus into error catastrophe.
journal_name
J Viroljournal_title
Journal of virologyauthors
Contreras AM,Hiasa Y,He W,Terella A,Schmidt EV,Chung RTdoi
10.1128/jvi.76.17.8505-8517.2002subject
Has Abstractpub_date
2002-09-01 00:00:00pages
8505-17issue
17eissn
0022-538Xissn
1098-5514journal_volume
76pub_type
杂志文章abstract::Transformation-defective (td) mutants with different sizes of genomic RNA were isolated from the Prague strain of Rous sarcoma virus, subgroup C(PR-C). All six td viruses (tdTYPR-C) isolated from a single UV-irradiated stock of PR-C (clone 2 of TYPR-C) had slightly longer RNA than did the ordinary class b RNA of tdB77...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.30.2.453-461.1979
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journal_title:Journal of virology
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doi:10.1128/JVI.00068-12
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.16.6.1391-1400.1975
更新日期:1975-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.1.530-542.1993
更新日期:1993-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.9.4390-4398.1990
更新日期:1990-09-01 00:00:00
abstract::Epstein-Barr Virus (EBV) generates a variety of viral microRNAs (miRNAs) by processing the BHRF1 and BamHI A rightward (BART) transcripts. BART miRNAs are expressed in all cells latently infected with EBV, but the functions of most BART miRNAs remain unknown. The results of a cell proliferation assay revealed that miR...
journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.2.1049-1058.2003
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.3.1855-1862.1996
更新日期:1996-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.20.3.646-657.1976
更新日期:1976-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.8.4705-4709.1992
更新日期:1992-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.5.4022-4031.1998
更新日期:1998-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.18.9993-10003.2003
更新日期:2003-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.56.1.194-200.1985
更新日期:1985-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01586-19
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.10.5507-5512.2004
更新日期:2004-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00124-13
更新日期:2013-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02346-08
更新日期:2009-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.1.379-389.1994
更新日期:1994-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2015-04-01 00:00:00
abstract::Many viruses express inhibitors of programmed cell death (apoptosis), thereby countering host defenses that would otherwise rapidly clear infected cells. To counter this, viruses such as adenoviruses and herpesviruses express recognizable homologs of the mammalian prosurvival protein Bcl-2. In contrast, the majority o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01115-12
更新日期:2012-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.21.13385-13398.2005
更新日期:2005-11-01 00:00:00
abstract::We have previously reported that infection of 9- to 13-day-old chicken embryos with RAV-1 results in rapid development of a novel B-cell lymphoma in which proviral insertion has activated expression of the c-myb gene (E. Pizer and E. H. Humphries, J. Virol. 63:1630-1640, 1989). The biological properties of these B-cel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.1.512-523.1992
更新日期:1992-01-01 00:00:00
abstract::Vaccines designed to elicit AIDS virus-specific CD8+ T cells should engender broad responses. Emerging data indicate that alternate reading frames (ARFs) of both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) encode CD8+ T cell epitopes, termed cryptic epitopes. Here, we show that SIV-speci...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2010-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2014-02-01 00:00:00
abstract::Varicella-zoster virus (VZV) is a highly species-specific herpesvirus that targets sensory ganglionic neurons. This species specificity has limited the study of many aspects of VZV pathogenesis, including neuronal infection. We report development of a highly efficient neuroblastoma cell model to study productive VZV i...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2011-08-01 00:00:00
abstract::Hepatitis C virus (HCV) is an enveloped positive-stranded RNA hepatotropic virus. HCV pseudoparticles infect liver-derived cells, supporting a model in which liver-specific molecules define HCV internalization. Three host cell molecules have been reported to be important entry factors or receptors for HCV internalizat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02286-07
更新日期:2008-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00808-15
更新日期:2015-07-01 00:00:00