Abstract:
:A tetracycline-regulated gene expression system and a panel of novel monoclonal antibodies were used to examine the subcellular localization, stability, and trans-cleavage competence of the hepatitis C virus (HCV) NS3-NS4A complex in inducible cell lines. The NS3 serine protease domain and the full-length NS3 protein expressed in the absence of the NS4A cofactor were diffusely distributed in the cytoplasm and nucleus. Coexpression of NS4A, however, directed NS3 to the endoplasmic reticulum (ER) or an ER-like modified compartment, as demonstrated by colocalization with 3,3'-dihexyloxacarbocyanine iodide, protein disulfide isomerase, and calnexin, as well as subcellular fractionation analyses. In addition, coexpression with NS4A dramatically increased the intracellular stability of NS3 (mean protein half-life of 26 versus 3 h) and allowed for NS4A-dependent trans-cleavage at the NS4B-NS5A junction. Deletion analyses revealed that the hydrophobic amino-terminal domain of NS4A was required for ER targeting of NS3. These results demonstrate the importance of studying HCV proteins in their biological context and define a well-characterized cell culture system for further analyses of the NS3-NS4A complex and the evaluation of novel antiviral strategies against hepatitis C.
journal_name
J Viroljournal_title
Journal of virologyauthors
Wölk B,Sansonno D,Kräusslich HG,Dammacco F,Rice CM,Blum HE,Moradpour Ddoi
10.1128/jvi.74.5.2293-2304.2000subject
Has Abstractpub_date
2000-03-01 00:00:00pages
2293-304issue
5eissn
0022-538Xissn
1098-5514journal_volume
74pub_type
杂志文章abstract::The largest tegument protein of herpes simplex virus 1 (HSV-1), UL36, contains a novel deubiquitinating activity embedded in it. All members of the Herpesviridae contain a homologue of HSV-1 UL36, the N-terminal segments of which show perfect conservation of those residues implicated in catalysis. For murine cytomegal...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.24.15582-15585.2005
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abstract::Temperature-sensitive (ts) mutants of vesicular stomatitis virus belonging to complementation groups I, II and IV inhibited the replication of wild-type vesicular stomatitis virus when mixed infections were carried out in BHK21 cells at 32, 37, and 39.5 C. The group IV mutant (ts G 41) was most effective in this regar...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.19.1.102-107.1976
更新日期:1976-07-01 00:00:00
abstract::Influenza viruses unable to express NS1 protein (delNS1) replicate poorly and induce large amounts of interferon (IFN). They are therefore considered candidate viruses for live-attenuated influenza vaccines. Their attenuated replication is generally assumed to result from the inability to counter the antiviral host re...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01725-12
更新日期:2012-11-01 00:00:00
abstract:UNLABELLED:Woodchuck hepatitis virus (WHV), a close relative of human hepatitis B virus (HBV), has been a key model for disease progression and clinical studies. Sequences of the assembly domain of WHV and HBV core proteins (wCp149 and hCp149, respectively) have 65% identity, suggesting similar assembly behaviors. We r...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01840-14
更新日期:2014-12-01 00:00:00
abstract::Levels of the p53 tumor suppressor protein are increased in human cytomegalovirus (HCMV)-infected cells and may be important for HCMV pathogenesis. In normal cells p53 levels are kept low due to an autoregulatory feedback loop where p53 activates the transcription of mdm2 and mdm2 binds and ubiquitinates p53, targetin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.8.3833-3843.2006
更新日期:2006-04-01 00:00:00
abstract::In an earlier study on minus-strand DNA synthesis catalyzed by murine leukemia virus reverse transcriptase, we described a prominent pause site near the polypurine tract (J. Guo, W. Wu, Z. Y. Yuan, K. Post, R. J. Crouch, and J. G . Levin, Biochemistry 34:5018-5029, 1995). We now report that pausing at this site is due...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.10.7132-7142.1996
更新日期:1996-10-01 00:00:00
abstract::Myeloid differentiation factor 88 (MyD88) is an essential adaptor protein in the Toll-like receptor-mediated innate signaling pathway, as well as in interleukin-1 receptor (IL-1R) and IL-18R signaling. The importance of MyD88 in the regulation of innate immunity to microbial pathogens has been well demonstrated. Howev...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01770-08
更新日期:2009-02-01 00:00:00
abstract::Rotavirus plus-strand RNAs not only direct protein synthesis but also serve as templates for the synthesis of the segmented double-stranded RNA (dsRNA) genome. In this study, we identified short-interfering RNAs (siRNAs) for viral genes 5, 8, and 9 that suppressed the expression of NSP1, a nonessential protein; NSP2, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.14.7763-7774.2004
更新日期:2004-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.10.4992-4997.2006
更新日期:2006-05-01 00:00:00
abstract::Flavopiridol, roscovitine, and other inhibitors of Cyclin-Dependent Kinases (CDK) inhibit the replication of a variety of viruses in vitro while proving nontoxic in human clinical trials of their effects against cancer. Consequently, these and other Pharmacological CDK inhibitors (PCIs) have been proposed as potential...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.17.9352-9365.2004
更新日期:2004-09-01 00:00:00
abstract:UNLABELLED:The interaction between viruses and immune cells of the host may lead to modulation of intracellular signaling pathways and to subsequent changes in cellular behavior that are of benefit for either virus or host. ERK1/2 (extracellular signal regulated kinase 1/2) signaling represents one of the key cellular ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02549-14
更新日期:2015-02-01 00:00:00
abstract::Despite successful antiretroviral therapy (ART), low-level viremia (LLV) may be intermittently detected in most HIV-infected patients. Longitudinal blood plasma and resting CD4(+) T cells were obtained from two patients on suppressive ART to investigate the source of LLV. Single-genome sequencing of HIV-1 env from LLV...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00284-11
更新日期:2011-05-01 00:00:00
abstract::Since most human immunodeficiency virus (HIV) infections are initiated following mucosal exposure to the virus, the anatomic containment or abortion of an HIV infection is likely to require vaccine-elicited cellular immune responses in those mucosal sites. Studying vaccine-elicited mucosal immune responses has been pr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.22.11484-11490.2002
更新日期:2002-11-01 00:00:00
abstract::Ebola virus (EBOV) infections result in aggressive hemorrhagic fever in humans, with fatality rates reaching 90% and with no licensed specific therapeutics to treat ill patients. Advances over the past 5 years have firmly established monoclonal antibody (MAb)-based products as the most promising therapeutics for treat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01548-18
更新日期:2019-02-19 00:00:00
abstract:UNLABELLED:Lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high mutation rate and low mutational tolerance of many RNA viruses. This approach uses mutagenic drugs to increase viral mutation rates and burden viral populations with mutations that reduce the number of infectious progeny. We inv...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03483-14
更新日期:2015-04-01 00:00:00
abstract::Herpes simplex virus (HSV) glycoprotein B (gB) is an integral part of the multicomponent fusion system required for virus entry and cell-cell fusion. Here we investigated the mechanism of viral neutralization by the monoclonal antibody (MAb) 2c, which specifically recognizes the gB of HSV type 1 (HSV-1) and HSV-2. Bin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01924-10
更新日期:2011-02-01 00:00:00
abstract::Intercellular adhesion molecule 1 (ICAM-1) mediates binding and entry of major group human rhinoviruses (HRVs). Whereas the entry pathway of minor group HRVs has been studied in detail and is comparatively well understood, the pathway taken by major group HRVs is largely unknown. Use of immunofluorescence microscopy, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01693-09
更新日期:2010-04-01 00:00:00
abstract::Picornaviruses are a family of positive-strand RNA viruses that are responsible for a variety of devastating human and animal diseases. An attenuated strain of mengovirus (vMC24) is serologically indistinguishable from the lethal murine wild-type mengovirus and encephalomyocarditis virus (EMCV). Immunogen-specific sti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.8.4914-4923.1995
更新日期:1995-08-01 00:00:00
abstract::The Middle East respiratory syndrome coronavirus (MERS-CoV) nonstructural protein 16 (nsp16) is an S-adenosyl-l-methionine (SAM)-dependent 2'-O-methyltransferase (2'-O-MTase) that is thought to methylate the ribose 2'-OH of the first transcribed nucleotide (N1) of viral RNA cap structures. This 2'-O-MTase activity is ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02217-16
更新日期:2017-02-14 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.10.8384-8391.1998
更新日期:1998-10-01 00:00:00
abstract:UNLABELLED:The distribution of vesicular stomatitis virus (VSV) nucleocapsids in the cytoplasm of infected cells was analyzed by scanning confocal fluorescence microscopy using a newly developed quantitative approach called the border-to-border distribution method. Nucleocapsids were located near the cell nucleus at ea...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00488-16
更新日期:2016-06-10 00:00:00
abstract::The 5'-untranslated regions (5' UTRs) of picornavirus genomes contain an internal ribosomal entry site (IRES) that promotes the end-independent initiation of translation. Picornavirus IRESs are classified into four structurally distinct groups, each with different initiation factor requirements. Here, we identify a fi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05862-11
更新日期:2012-02-01 00:00:00
abstract:UNLABELLED:Oncogenesis is frequently accompanied by the activation of specific metabolic pathways. One such pathway is fatty acid biosynthesis, whose induction is observed upon transformation of a wide variety of cell types. Here, we explored how defined oncogenic alleles, specifically the simian virus 40 (SV40) T anti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03671-14
更新日期:2015-06-01 00:00:00
abstract::Hepatitis delta virus (HDV), a single-stranded RNA virus, bears a single coding region whose product, the hepatitis delta antigen (HDAg), is expressed in two isoforms, small (S-HDAg) and large (L-HDAg). S-HDAg is required for replication of HDV, while L-HDAg inhibits viral replication and is required for the envelopme...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.11.5329-5336.2000
更新日期:2000-06-01 00:00:00
abstract::Primary sympathetic neuronal cultures were maintained for up to 5 weeks after inoculation with herpes simplex virus (HSV) without evidence of viral infection. Upon deprivation of nerve growth factor, the cultures produced infectious HSV, indicating that the cultures harbored latent HSV. This study demonstrates a funct...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.7.2311-2315.1987
更新日期:1987-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03119-15
更新日期:2015-12-23 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.16.10678-10689.2005
更新日期:2005-08-01 00:00:00
abstract::The smallpox vaccine is the prototypic vaccine, yet the viral targets critical for vaccine-mediated protection remain unclear in humans. We have produced protein microarrays of a near-complete vaccinia proteome and used them to determine the major antigen specificities of the human humoral immune response to the small...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.18.11724-11733.2005
更新日期:2005-09-01 00:00:00
abstract::Little is known about the biological significance of human adenovirus type 5 (Ad5) E1A in vivo. However, Ad5 E1A is well defined in vitro and can be detected frequently in the lungs of patients with pulmonary disease. Transgenic expression of the Ad5 E1A gene targeted to the mouse lung reveals distinct biological effe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.17.8910-8919.2002
更新日期:2002-09-01 00:00:00
abstract::We provide here new insights into rotavirus (RRV) pathogenicity by showing that RRV infection promotes structural and functional injuries localized at the tight junctions (TJ) in the cell-cell junctional complex of cultured polarized human intestinal Caco-2 cells forming monolayers. RRV infection resulted in a progres...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.10.4645-4651.2000
更新日期:2000-05-01 00:00:00