Abstract:
:The active template for RNA synthesis for vesicular stomatitis virus (VSV) and other negative-strand viruses is the RNA genome in association with the nucleocapsid (N) protein. The N protein molecules sequester the genomic RNA and are linked together by a network of noncovalent interactions. We previously demonstrated that mutations predicted to weaken interactions between adjacent N protein molecules altered the levels of RNA synthesis directed from subgenomic ribonucleoprotein (RNP) templates. To determine if these mutations affect virus replication, recombinant viruses containing single-amino-acid substitutions in the N protein were recovered. Four mutations altered transcription and genome replication levels, perturbed viral protein synthesis, and inhibited virus replication. Selective pressure for improved virus replication was applied by eight sequential passages. After five passages, virus replication improved and RNA synthesis recovered concomitantly with the restoration of the protein molar ratios to near-wild-type levels. Genome sequences were compared before and after passage to determine whether compensatory mutations were selected and to potentially identify interactions between N protein molecules or between the RNP template and the viral polymerase. Improved virus replication correlated with the selection of additional mutations located in cis-acting transcriptional regulatory sequences at the gene junctions of the genome rather than in coding sequences, with one exception. The engineered N gene mutations perturbed mRNA and protein expression levels, but the selection of modified transcriptional regulatory sequences with passage facilitated the restoration of wild-type protein expression by modulating transcription levels, reflecting the adaptability and versatility of gene regulation by transcriptional control.
journal_name
J Viroljournal_title
Journal of virologyauthors
Harouaka D,Wertz GWdoi
10.1128/JVI.01238-12subject
Has Abstractpub_date
2012-10-01 00:00:00pages
11266-75issue
20eissn
0022-538Xissn
1098-5514pii
JVI.01238-12journal_volume
86pub_type
杂志文章abstract::The simian virus 40 (SV40) large tumor antigen (Tag) is a virus-encoded oncoprotein which is the target of a strong cytotoxic T-lymphocyte (CTL) response. Three immunodominant H-2(b)-restricted epitopes, designated epitopes I, II/III, and IV, have been defined. We investigated whether induction of CTLs directed agains...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.7.5981-5993.1999
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abstract::Transcription of the terminal protein (TP) gene of Epstein-Barr virus (EBV) in Burkitt's lymphoma cells, in EBV-negative Burkitt's lymphoma cells converted with transformation-defective (P3HR1) and transformation-competent (B95-8, AG876) EBV strains, and in EBV-immortalized cell lines was studied. A TP1 cDNA probe spa...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.1.415-423.1991
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pub_type: 杂志文章
doi:10.1128/JVI.02408-10
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.3.1359-1368.2002
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.5.4104-4115.1998
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.10.5266-5270.2002
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.23.11686-11699.2001
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.2.686-690.1990
更新日期:1990-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01316-10
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.8.3555-3565.2000
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.37.1.478-482.1981
更新日期:1981-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.6.2913-2923.2006
更新日期:2006-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.26.2.243-248.1978
更新日期:1978-05-01 00:00:00
abstract::GS-8374 is a potent HIV protease inhibitor (PI) with a unique diethyl-phosphonate moiety. Due to a balanced contribution of enthalpic and entropic components to its interaction with the protease (PR) active site, the compound retains activity against HIV mutants with high-level multi-PI resistance. We report here the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01211-12
更新日期:2013-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.39.3.903-913.1981
更新日期:1981-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.10.5914-5923.1992
更新日期:1992-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.22.12638-12646.2004
更新日期:2004-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.44.2.595-602.1982
更新日期:1982-11-01 00:00:00
abstract:UNLABELLED:Protease is essential for retroviral replication, and protease inhibitors (PI) are important for treating HIV infection. HIV-2 exhibits intrinsic resistance to most FDA-approved HIV-1 PI, retaining clinically useful susceptibility only to lopinavir, darunavir, and saquinavir. The mechanisms for this resistan...
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.63.10.4362-4369.1989
更新日期:1989-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00235-17
更新日期:2017-06-09 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00293-12
更新日期:2012-08-01 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:2000-01-01 00:00:00
abstract::Toroviruses (family Coronaviridae, order Nidovirales) are enveloped, positive-stranded RNA viruses that have been implicated in enteric disease in cattle and possibly in humans. Despite their potential veterinary and clinical relevance, little is known about torovirus epidemiology and molecular genetics. Here, we pres...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.17.9567-9577.2003
更新日期:2003-09-01 00:00:00
abstract::DBA/2 mice carry a single endogenous ecotropic murine leukemia provirus designated Emv-3. Although this provirus appears to be nondefective by genomic restriction enzyme mapping, weanling mice do not produce virus and only about one-third of adult mice ever express virus. 5-Iododeoxyuridine and 5-azacytidine, two pote...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.2.479-487.1988
更新日期:1988-02-01 00:00:00
abstract::Two strains of minute virus of mice (MVM) show different host cell specificities. The prototype strain MVM(p) grows in fibroblasts, whereas the immunosuppressive variant MVM(i) grows in T lymphocytes. In this study, we have mapped on the viral genome a cell type-specific determinant: it is located between 69 and 85 ma...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.2.552-557.1988
更新日期:1988-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.8.4130-4136.1991
更新日期:1991-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.10.5735-5743.1992
更新日期:1992-10-01 00:00:00
abstract:UNLABELLED:During the chronic phase of HIV-1 infection, polyfunctional CD8+ T cell responses, which are characterized by a high frequency of cells able to secrete multiple cytokines simultaneously, are associated with lower virus loads and slower disease progression. This relationship may arise for different reasons. P...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00647-14
更新日期:2014-09-01 00:00:00
abstract::Cloned avian leukosis viral DNAs were mutagenized in the long terminal repeat, in the leader sequence for env mRNA, and at the poly-env junction. The effect of these mutations in the viral DNA upon its ability to direct virus production or env mRNA synthesis was analyzed by microinjecting the mutant DNAs into chicken ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.43.2.503-510.1982
更新日期:1982-08-01 00:00:00