Abstract:
:Cell-based hepatitis C virus (HCV) replicon systems have provided a means for understanding HCV replication mechanisms and for testing new antiviral agents. We describe here a mathematical model of HCV replication that assumes that the translation of the HCV polyprotein occurs in the cytoplasm, that HCV RNA synthesis occurs in vesicular-membrane structures, and that the strategy of replication involves a double-stranded RNA intermediate. Our results shed light on the intracellular dynamics of subgenomic HCV RNA replication from transfection to steady state within Huh-7 cells. We predict the following: (i) about 6 x 10(3) ribosomes are involved in generating millions of HCV NS5B-polymerase molecules in a Huh-7 cell, (ii) the observed 10:1 asymmetry of plus- to minus-strand RNA levels can be explained by a higher-affinity (200-fold) interaction of HCV NS5B polymerase-containing replication complexes with HCV minus-strand RNA over HCV plus-strand RNA in order to initiate synthesis, (iii) the latter higher affinity can also account for the observed approximately 6:1 plus-strand/minus-strand ratio in vesicular-membrane structures, and (iv) the introduction of higher numbers of HCV plus-strand RNA by transfection leads to faster attainment of steady-state but does not change the steady-state HCV RNA level. Fully permissive HCV replication systems have been developed, and the model presented here is a first step toward building a comprehensive model for complete HCV replication. Moreover, the model can serve as an important tool in understanding HCV replication mechanisms and should prove useful in designing and evaluating new antivirals against HCV.
journal_name
J Viroljournal_title
Journal of virologyauthors
Dahari H,Ribeiro RM,Rice CM,Perelson ASdoi
10.1128/JVI.01304-06subject
Has Abstractpub_date
2007-01-01 00:00:00pages
750-60issue
2eissn
0022-538Xissn
1098-5514pii
JVI.01304-06journal_volume
81pub_type
杂志文章abstract::Cytotoxic T lymphocytes (CTL) play an important role in recovery from a number of viral infections. They are also implicated in virus-induced immunopathology as best demonstrated in lymphocytic choriomeningitis virus (LCMV) infection of adult immunocompetent mice. In the present study, the structure of the T-cell rece...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.12.5919-5926.1990
更新日期:1990-12-01 00:00:00
abstract:UNLABELLED:As a herpesvirus, Epstein-Barr virus (EBV) establishes a latent infection that can periodically undergo reactivation, resulting in lytic replication and the production of new infectious virus. Latent membrane protein-1 (LMP1), the principal viral oncoprotein, is a latency-associated protein implicated in reg...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00711-15
更新日期:2015-08-01 00:00:00
abstract::Previous findings of low levels of reverse transcriptase (RT) activity in chick cell-derived measles and mumps vaccines showed this activity to be associated with virus particles containing RNA of both subgroup E endogenous avian leukosis viruses (ALV-E) and endogenous avian viruses (EAV). These particles originate fr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.8.3605-3612.2001
更新日期:2001-04-01 00:00:00
abstract::Type C RNA virus(es) was readily released from primary lymphosarcoma cell cultures of WH/J rabbits after induction with halogenated pyrimidines. The virus contained an RNA-directed DNA polymerase and the p30 structural protein. The rabbit virus RNA-directed DNA polymerase and p30 protein shared antigenic homologies wi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.27.2.313-319.1978
更新日期:1978-08-01 00:00:00
abstract::Coronaviruses generally have a narrow host range, infecting one or just a few species. Using targeted RNA recombination, we constructed a mutant of the coronavirus mouse hepatitis virus (MHV) in which the ectodomain of the spike glycoprotein (S) was replaced with the highly divergent ectodomain of the S protein of fel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.3.1393-1406.2000
更新日期:2000-02-01 00:00:00
abstract:UNLABELLED:The vaccinia virus (VACV) E3 protein has been shown to be important for blocking activation of the cellular innate immune system and allowing viral replication to occur unhindered. Mutation or deletion of E3L severely affects viral host range and pathogenesis. While the monkeypox virus (MPXV) genome encodes ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00304-15
更新日期:2015-10-01 00:00:00
abstract::In the search for effective immunologic interventions to prevent and treat HIV-1 infection, standardized reference reagents are a cost-effective way to maintain robustness and reproducibility among immunological assays. To support planned and ongoing studies where clade C predominates, here we describe three virus pan...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00991-17
更新日期:2017-09-12 00:00:00
abstract::Satellite RNAs are the smallest infectious agents whose replication is thought to be completely dependent on their helper virus (HV). Here we report that, when expressed autonomously in the absence of HV, a variant of satellite RNA (satRNA) associated with Cucumber mosaic virus strain Q (Q-satRNA) has a propensity to ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00018-12
更新日期:2012-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.6.2808-2818.2004
更新日期:2004-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.13.5985-5997.2001
更新日期:2001-07-01 00:00:00
abstract::Inhibition of histone deacetylase (HDAC) activity induces growth arrest, differentiation, and, in certain cell types, apoptosis. FR901228, FK228, or depsipeptide, is an HDAC inhibitor effective in T-cell lymphomas. Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) and remains incurab...
journal_title:Journal of virology
pub_type: 杂志文章,收录出版
doi:10.1128/jvi.78.9.4582-4590.2004
更新日期:2004-05-01 00:00:00
abstract::Here, we report a novel porcine circovirus type 2a (PCV2a) strain with 11 nucleotides (nt) inserted in the origin of genome replication (Ori). This is the first report of a PCV2a strain with nucleotide insertion in Ori. Our study will help further epidemiological studies and extend our knowledge of evolutionary charac...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00760-12
更新日期:2012-06-01 00:00:00
abstract::Immune activation is a major characteristic of human immunodeficiency virus type 1 (HIV-1) infection and a strong prognostic factor for HIV-1 disease progression. The underlying mechanisms leading to immune activation in viremic HIV-1 infection, however, are not fully understood. Here we show that, following the initi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00421-07
更新日期:2007-08-01 00:00:00
abstract::Varicella-zoster virus (VZV) is distinguished from herpes simplex virus type 1 (HSV-1) by the fact that cell-to-cell fusion and syncytium formation require only gH and gL within a transient-expression system. In the HSV system, four glycoproteins, namely, gH, gL, gB, and gD, are required to induce a similar fusogenic ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.19.9483-9492.2001
更新日期:2001-10-01 00:00:00
abstract::Immunity to human immunodeficiency virus virion-like structures or a polyprotein has been examined after DNA immunization with Rev-independent expression vectors. A Gag-Pol fusion protein stimulated cytotoxic T lymphocyte and antibody responses to Gag and Pol, while a Gag-Pol pseudoparticle did not elicit substantial ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.10.4947-4951.2001
更新日期:2001-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.4.3495-3500.1998
更新日期:1998-04-01 00:00:00
abstract::Transgenic (Tg) mice expressing full-length bovine prion protein (BoPrP) serially propagate bovine spongiform encephalopathy (BSE) prions without posing a transmission barrier. These mice also posed no transmission barrier for Suffolk sheep scrapie prions, suggesting that cattle may be highly susceptible to some sheep...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.9.5259-5271.2005
更新日期:2005-05-01 00:00:00
abstract::Hepatitis delta virus (HDV) replicates its genome in the nucleus of an infected cell. However, an unsolved problem has been the identification in the cytoplasm of a putative mRNA for the synthesis of the only virus-coded protein, the delta antigen. We now report the characterization of an 800-base RNA that is cytoplas...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.7.3192-3198.1990
更新日期:1990-07-01 00:00:00
abstract::Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has traditionally circulated in Africa and Asia, causing human febrile illness accompanied by severe, chronic joint pain. In Africa, epidemic emergence of CHIKV involves the transition from an enzootic, sylvatic cycle involving arboreal mosquito vectors and nonhu...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01603-09
更新日期:2010-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.7.3928-3931.1991
更新日期:1991-07-01 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:2003-11-01 00:00:00
abstract::Cells that express glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) resist infection by HSV-1 and HSV-2 because of interference with viral penetration. The results presented here show that both HSV-1 and HSV-2 gD can mediate interference and that various HSV-1 and HSV-2 strains differ in sensitivity to this ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.8.5171-5176.1995
更新日期:1995-08-01 00:00:00
abstract::The Kaposi's sarcoma-associated herpesvirus (KSHV) (or human herpesvirus 8) open reading frame (ORF) K15 encodes a putative integral transmembrane protein in the same genomic location as latent membrane protein 2A of Epstein-Barr virus. Ectopic expression of K15 in cell lines revealed the presence of several different...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.2.802-816.2002
更新日期:2002-01-01 00:00:00
abstract::The pregenomic RNA (pgRNA) of hepatitis B virus (HBV) serves as the messenger for both core and P proteins, with the downstream P gene translated by ribosomal leaky scanning. HBV replication begins with packaging of the pgRNA and P protein into core protein particles, followed by conversion of RNA into DNA. Genotype G...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05583-11
更新日期:2011-12-01 00:00:00
abstract::Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism. The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG). Binding of LASV depends on DG's tissue-specific posttranslation...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01613-17
更新日期:2018-02-12 00:00:00
abstract::CH/S is a virulent porcine epidemic diarrhea virus (PEDV) strain and is used as the virulent strain to evaluate the protection rates of vaccines against PEDV infection in China. Here, we report the complete genome sequence of strain CH/S, which may aid in understanding the molecular characteristics of this strain. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06024-11
更新日期:2011-11-01 00:00:00
abstract::A prerequisite for understanding the molecular function of the human cytomegalovirus (HCMV) gH (UL75)-gL (UL115) complex is a detailed knowledge of the structure of this complex in its functional form, as it is present in mature virions. The gH protein is known to be a component of a 240-kDa envelope complex designate...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.7.5391-5398.1997
更新日期:1997-07-01 00:00:00
abstract::The novel low-pathogenic avian influenza A H7N9 viruses (LPAI H7N9 viruses) have been a threat to public health since their emergence in 2013 because of the high rates of mortality and morbidity that they cause. Recently, highly pathogenic variants of these avian influenza A H7N9 viruses (HPAI H7N9 viruses) have emerg...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01277-17
更新日期:2017-11-14 00:00:00
abstract::Pathogens such as HIV-1, with their minimalist genomes, must navigate cellular networks and rely on hijacking and manipulating the host machinery for successful replication. Limited overlap of host factors identified as vital for pathogen replication may be explained by considering that pathogens target, rather than s...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.03684-14
更新日期:2015-05-01 00:00:00
abstract::DNA was extracted from [(3)H]thymidine-labeled Marek's disease virus (MDV) and purified by two cycles of CsCl gradient centrifugation in a fixed-angle rotor. The DNA was transcribed in vitro into (32)P-labeled complementary RNA (cRNA). MDV cRNA did not hybridize with DNA from chicken embryo fibroblast cultures or from...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.4.841-846.1973
更新日期:1973-10-01 00:00:00