Abstract:
:The NS3 protein of hepatitis C virus (HCV) possesses protease activity responsible for the proteolytic cleavage of the viral polyprotein at the junctions of nonstructural proteins downstream of NS3. The NS3 protein was also found to be internally cleaved. In this study, we demonstrated that internal cleavages occurred on the NS3 protein of genotype 1b in the presence of NS4A, both in culture cells and with a mouse model system. No internal cleavage products were detected with the NS3 and NS4A proteins of genotype 2a. Three potential cleavage sites were detected in the NS3 protein (genotype 1b), with IPT(402)|S being the major one. The internal cleavage requires the polyprotein processing activity of NS3 protease, but when supplemented in trans, the internal cleavage efficiency is reduced. In addition, several mutations in NS4A disrupted the internal cleavage of NS3 but did not affect polyprotein processing, indicating that NS4A contributes differently to these two proteolytic activities. Furthermore, Ile-25, Val-26, and Ile-29 of the NS4A protein, important for the NS4A-dependent internal cleavages, were also shown to be critical for the transforming activity of NS3, but mutations at these critical residues resulted only in a slight increase of HCV replicating efficiency. The internal cleavage-associated enhancement of the transforming activity of NS3 was reduced when a T402A substitution at the major internal cleavage site was introduced. The multiple roles of NS4A in viral multiplication and pathogenesis make NS4A an ideal molecular target for HCV therapy.
journal_name
J Viroljournal_title
Journal of virologyauthors
Kou YH,Chang MF,Wang YM,Hung TM,Chang SCdoi
10.1128/JVI.00348-07subject
Has Abstractpub_date
2007-08-01 00:00:00pages
7999-8008issue
15eissn
0022-538Xissn
1098-5514pii
JVI.00348-07journal_volume
81pub_type
杂志文章abstract::Replication of poliovirus (PV) is restricted to a few sites, including the brain and spinal cord. However, this neurotropism is not conserved in cultured cells. Monkey kidney cells become susceptible to PV infection after cultivation in vitro, and cell lines of monolayer cultures from almost any tissue of primates are...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.9.4313-4325.2006
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abstract::Candidate foot-and-mouth disease (FMD) DNA vaccines designed to produce viral capsids lacking infectious viral nucleic acid were evaluated. Plasmid DNAs containing a portion of the FMDV genome coding for the capsid precursor protein (P1-2A) and wild-type or mutant viral proteinase 3C (plasmids P12X3C or P12X3C-mut, re...
journal_title:Journal of virology
pub_type: 杂志文章
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abstract::Chick embryo cells became more sensitive to the action of interferon the longer they remained in culture. This phenomenon was found even before confluency had been reached. The relative insensitivity of newly seeded cells was not due to a loss of receptors. Cells synthesizing deoxyribonucleic acid (DNA) at a high rate...
journal_title:Journal of virology
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doi:10.1128/JVI.4.1.7-11.1969
更新日期:1969-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.32.1.345-349.1979
更新日期:1979-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.58.1.212-215.1986
更新日期:1986-04-01 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:1998-01-01 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:1973-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1999-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章,随机对照试验
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更新日期:2015-07-01 00:00:00
abstract::The relative antigenicity of the individual herpes simplex virus type 1 (KOS) glycoproteins gC and gB was analyzed in BALB/c mice by using KOS mutants altered in their ability to present these antigens on cell surface membranes during infection. The mutants employed were as follows: syn LD70 , a non-temperature-sensit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.3.805-812.1984
更新日期:1984-06-01 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:2011-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.11.6496-6501.1992
更新日期:1992-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.4.1669-1676.1989
更新日期:1989-04-01 00:00:00
abstract::Six phages were isolated from sewage and from a lysogenic strain. Three of them, belonging to a new morphological group, had contractile tails and elongated heads with axial ratios of 2.4:1. Two phages, possessing short tails and very long heads with axial ratios of 3.5:1, were new isolates of an extremely rare group....
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pub_type: 杂志文章
doi:10.1128/JVI.13.3.706-711.1974
更新日期:1974-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.10.4842-4850.1990
更新日期:1990-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06216-11
更新日期:2012-02-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2015-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.40.3.848-860.1981
更新日期:1981-12-01 00:00:00
abstract::We report several biological activities of a synthetic peptide whose sequence contains the highly conserved region of feline leukemia virus transmembrane protein (TM) synthetically linked to another short TM-derived sequence particularly rich in polar positive residues. This 29-amino-acid peptide blocked [3H]thymidine...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.4.1429-1436.1990
更新日期:1990-04-01 00:00:00
abstract::The complete genome sequences of two Sulfolobus spindle-shaped viruses (SSVs) from acidic hot springs in Kamchatka (Russia) and Yellowstone National Park (United States) have been determined. These nonlytic temperate viruses were isolated from hyperthermophilic Sulfolobus hosts, and both viruses share the spindle-shap...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.4.1954-1961.2004
更新日期:2004-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.5.2862-2870.1993
更新日期:1993-05-01 00:00:00
abstract::Feline panleukopenia virus (FPV) and its host range variant, canine parvovirus (CPV), can bind the feline transferrin receptor (TfR), while only CPV binds to the canine TfR. Introducing two CPV-specific changes into FPV (at VP2 residues 93 and 323) endowed that virus with the canine TfR binding property and allowed ca...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.18.10099-10105.2003
更新日期:2003-09-01 00:00:00
abstract::A new subgroup of avian leukosis virus (ALV) that includes a unique env gene, designated J, was identified recently in England. Sequence analysis of prototype English isolate HPRS-103 revealed several other unique genetic characteristics of this strain and provided information that it arose by recombination between ex...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.12.10301-10304.1998
更新日期:1998-12-01 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:2004-06-01 00:00:00
abstract::Arenaviruses are rodent-borne viruses with a bisegmented RNA genome. A genetically unique arenavirus, Lujo virus, was recently discovered as the causal agent of a nosocomial outbreak of acute febrile illness with hemorrhagic manifestations in Zambia and South Africa. The outbreak had a case fatality rate of 80%. A rev...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01144-12
更新日期:2012-10-01 00:00:00
abstract::Analysis of large and small plaque mutants of simian virus 40 using antisera prepared against each has revealed quantitative and possibly qualitative antigenic differences for each plaque type. A sensitive micro radioisotope precipitation test permitted evaluation of immunochemical similarities and differences of caps...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.3.1.17-24.1969
更新日期:1969-01-01 00:00:00
abstract::In the immunocompetent host, primary cytomegalovirus (CMV) infection is resolved by the immune response without causing overt disease. The viral genome, however, is not cleared but is maintained in a latent state that entails a risk of virus recurrence and consequent organ disease. By using murine CMV as a model, we h...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.3.1797-1804.1998
更新日期:1998-03-01 00:00:00