Abstract:
UNLABELLED:Aminoquinolines and piperazines, linked or not, have been used successfully to treat malaria, and some molecules of this family also exhibit antiviral properties. Here we tested several derivatives of 4-aminoquinolines and piperazines for their activity against hepatitis C virus (HCV). We screened 11 molecules from three different families of compounds, and we identified anti-HCV activity in cell culture for six of them. Of these, we selected a compound (B5) that is currently ending clinical phase I evaluation for neurodegenerative diseases. In hepatoma cells, B5 inhibited HCV infection in a pangenotypic and dose-dependent manner, and its antiviral activity was confirmed in primary hepatocytes. B5 also inhibited infection by pseudoparticles expressing HCV envelope glycoproteins E1 and E2, and we demonstrated that it affects a postattachment stage of the entry step. Virus with resistance to B5 was selected by sequential passage in the presence of the drug, and reverse genetics experiments indicated that resistance was conferred mainly by a single mutation in the putative fusion peptide of E1 envelope glycoprotein (F291I). Furthermore, analyses of the effects of other closely related compounds on the B5-resistant mutant suggest that B5 shares a mode of action with other 4-aminoquinoline-based molecules. Finally, mice with humanized liver that were treated with B5 showed a delay in the kinetics of the viral infection. In conclusion, B5 is a novel interesting anti-HCV molecule that could be used to decipher the early steps of the HCV life cycle. IMPORTANCE:In the last 4 years, HCV therapy has been profoundly improved with the approval of direct-acting antivirals in clinical practice. Nevertheless, the high costs of these drugs limit access to therapy in most countries. The present study reports the identification and characterization of a compound (B5) that inhibits HCV propagation in cell culture and is currently ending clinical phase I evaluation for neurodegenerative diseases. This molecule inhibits the HCV life cycle by blocking virus entry. Interestingly, after selection of drug-resistant virus, a resistance mutation in the putative fusion peptide of E1 envelope glycoprotein was identified, indicating that B5 could be used to further investigate the fusion mechanism. Furthermore, mice with humanized liver treated with B5 showed a delay in the kinetics of the viral infection. In conclusion, B5 is a novel interesting anti-HCV molecule that could be used to decipher the early steps of the HCV life cycle.
journal_name
J Viroljournal_title
Journal of virologyauthors
Vausselin T,Séron K,Lavie M,Mesalam AA,Lemasson M,Belouzard S,Fénéant L,Danneels A,Rouillé Y,Cocquerel L,Foquet L,Rosenberg AR,Wychowski C,Meuleman P,Melnyk P,Dubuisson Jdoi
10.1128/JVI.00404-16subject
Has Abstractpub_date
2016-09-12 00:00:00pages
8422-34issue
19eissn
0022-538Xissn
1098-5514pii
JVI.00404-16journal_volume
90pub_type
杂志文章abstract::To map the DNA-binding domain of polyomavirus large T antigen, we constructed a set of plasmids coding for unidirectional carboxy- or amino-terminal deletion mutations in the large T antigen. Analysis of origin-specific DNA binding by mutant proteins expressed in Cos-1 cells revealed that the C-terminal boundary of th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.12.6998-7003.1991
更新日期:1991-12-01 00:00:00
abstract::CD4+ T-cell depletion in AIDS patients involves induction of apoptosis in human immunodeficiency virus (HIV)-infected and noninfected T cells. The HIV type 1 (HIV-1)-transactivating protein Tat enhances apoptosis and activation-induced cell death (AICD) of human T cells. This effect is mediated by the CD95 (APO-1/Fas)...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.9.6502-6507.1996
更新日期:1996-09-01 00:00:00
abstract::CD8(+) cytotoxic T lymphocytes (CTL) play a key role in the control of many virus infections, and the need for vaccines to elicit strong CD8(+) T-cell responses in order to provide optimal protection in such infections is increasingly apparent. However, the mechanisms involved in the induction and maintenance of CD8(+...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.9.7440-7449.1998
更新日期:1998-09-01 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::Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality. Previous studies have suggested that T-cell responses may contribute to RSV immunopathology, which could be driven by dendritic cells (DCs). DCs are productively infected by RSV, and during RSV infections, there is an increase of DCs in the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01273-10
更新日期:2010-12-01 00:00:00
abstract::In view of the concern over potential infection hazards in the use of porcine tissues and organs for xenotransplantation to humans, we investigated the diversity of porcine endogenous retrovirus (PERV) genomes in the DNA of domestic pigs and related species. In addition to the three known envelope subgroups of infecti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.6.2771-2775.2001
更新日期:2001-03-01 00:00:00
abstract::The internal deletion mutant (DI-LT) derived from the heat-resistant strain of vesicular stomatitis virus synthesizes an aberrant polyadenylated mRNA (G*) containing a transcript of the partially deleted polymerase gene covalently linked to the 3' end of the glycoprotein message (R. C. Herman and R. A. Lazzarini, J. V...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.46.3.709-717.1983
更新日期:1983-06-01 00:00:00
abstract::The activity of phosphatidylinositol 4-kinase class III beta (PI4KIIIβ) has been shown to be required for the replication of multiple picornaviruses; however, it is unclear whether a physical association between PI4KIIIβ and the viral replication machinery exists and, if it does, whether association is necessary. We e...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06778-11
更新日期:2012-04-01 00:00:00
abstract::The combinatorial nature of genetic recombination can potentially provide organisms with immediate access to many more positions in sequence space than can be reached by mutation alone. Recombination features particularly prominently in the evolution of a diverse range of viruses. Despite rapid progress having been ma...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02152-08
更新日期:2009-03-01 00:00:00
abstract::A region of the herpesvirus saimiri genome encoding an mRNA with two open reading frames (ORFs) has been identified to be essential for transformation of T cells. Deletion of either ORF resulted in the loss of transforming ability. ORF-1 has been shown to code for a collagen-like oncoprotein. This study shows for the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.7.4495-4499.1995
更新日期:1995-07-01 00:00:00
abstract::The E5 protein of human papillomavirus type 16 is a small, hydrophobic protein that localizes predominantly to membranes of the endoplasmic reticulum (ER). To define the orientation of E5 in these membranes, we employed a differential, detergent permeabilization technique that makes use of the ability of low concentra...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01968-09
更新日期:2010-02-01 00:00:00
abstract::The binding of cyclophilin A (CypA) to the human immunodeficiency virus type 1 (HIV-1) capsid protein (CA protein) is required soon after virus entry into natural target cells. In Jurkat T lymphocytes, disrupting CypA-CA interaction either by cyclosporine (Cs) treatment or by alteration (e.g., P90A) of the CA inhibits...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00682-09
更新日期:2009-11-01 00:00:00
abstract:UNLABELLED:Susceptibility or resistance to prion infection in humans and animals depends on single prion protein (PrP) amino acid substitutions in the host, but the agent's modulating role has not been well investigated. Compared to disease incubation times in wild-type homozygous ARQ/ARQ (where each triplet represents...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02316-15
更新日期:2015-10-28 00:00:00
abstract::Adenovirus gene therapy is a promising tool in the clinical treatment of many genetic and acquired diseases. However, it has also caused pathogenic effects in organs such as the liver. The redox-sensitive transcription factors AP-1 and NF-kappaB have been implicated in these effects. To study the mechanisms of adenovi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.1.355-363.2002
更新日期:2002-01-01 00:00:00
abstract::We examined the 5' ends of Hantaan virus (HTN) genomes and mRNAs to gain insight into the manner in which these chains were initiated. Like those of all members of the family Bunyaviridae described so far, the HTN mRNAs contained 5' terminal extensions that were heterogeneous in both length and sequence, presumably be...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5754-5762.1995
更新日期:1995-09-01 00:00:00
abstract::The development of cancer vaccines requires approaches to induce expansion and functional differentiation of tumor antigen-specific cytotoxic T lymphocyte (CTL) effectors which posses cytolytic capability and produce cytokines. Efficient induction of such cells is hindered by the poor immunogenicity of tumor antigens ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.13.7411-7424.2003
更新日期:2003-07-01 00:00:00
abstract:UNLABELLED:Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious, economically important viral disease in many countries. The E(rns) and E2 envelope glycoproteins are responsible for the binding to and entry into the host cell by CSFV. To date, only one cellular r...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00019-15
更新日期:2015-05-01 00:00:00
abstract:UNLABELLED:The Nairovirus genus of the Bunyaviridae family contains serious human and animal pathogens classified within multiple serogroups and species. Of these serogroups, the Crimean-Congo hemorrhagic fever virus (CCHFV) serogroup comprises sole members CCHFV and Hazara virus (HAZV). CCHFV is an emerging zoonotic v...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00661-16
更新日期:2016-09-29 00:00:00
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 ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01304-06
更新日期:2007-01-01 00:00:00
abstract::The bovine papillomavirus E5 gene encodes a 44-amino-acid, homodimeric transmembrane protein that is the smallest known transforming protein. The E5 protein transforms cultured fibroblasts by forming a stable complex with the endogenous platelet-derived growth factor (PDGF) beta receptor through transmembrane and juxt...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.4.3264-3272.1999
更新日期:1999-04-01 00:00:00
abstract::Inbred LSH hamster brain cells were transformed in vitro by the GS strain of BK virus (BKV), and transplantable tumors classified as undifferentiated glioblastomas were induced in the syngeneic host. The viral status in the transformed cells, designated LSH-BR-BK, was established. About 46 genome equivalents per cell ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.40.1.276-284.1981
更新日期:1981-10-01 00:00:00
abstract::Many replication events are involved in the influenza A virus life cycle, and they are accomplished by different virus proteins with specific functions. However, because the size of the influenza virus genome is limited, the virus uses different mechanisms to express multiple viral proteins from a single gene segment....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02656-12
更新日期:2013-03-01 00:00:00
abstract::JC virus (JCV), along with other members of the polyomavirus family, encodes a class of highly conserved proteins, T antigens, that are capable of inducing aneuploidy in cultured cells. We have previously isolated T-antigen DNA variants of JCV from both colon cancer tissues and the corresponding nonneoplastic gastroin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.4.1996-2001.2001
更新日期:2001-02-01 00:00:00
abstract:UNLABELLED:Mumps virus (MuV), a paramyxovirus containing a negative-sense nonsegmented RNA genome, is a human pathogen that causes an acute infection with symptoms ranging from parotitis to mild meningitis and severe encephalitis. Vaccination against mumps virus has been effective in reducing mumps cases. However, rece...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03673-13
更新日期:2014-04-01 00:00:00
abstract::Production of a vesicular stomatitis virus spike protein G (VSVG)-pseudotyped lentiviral expression vector in HEK293 cells decreased on overexpression of low-density lipoprotein receptor (LDLR) but not that of ICAM1 or TfR1. Reverse transcription-quantitative PCR (RT-qPCR) revealed a reduction in vector RNA as a funct...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01869-15
更新日期:2015-11-01 00:00:00
abstract::The development of immunization strategies to protect against ocular infection with herpes simplex virus 1 (HSV-1) must address the issue of the effects of the strategy on the establishment of latency in the trigeminal ganglia (TG). It is the reactivation of this latent virus that can cause recurrent disease and corne...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00913-14
更新日期:2014-07-01 00:00:00
abstract::Ten bacteriophages that attack and lyse saprophytic strains of Bdellovibrio bacteriovorus were isolated. Morphological, serological, and host-range studies revealed that there were four different bdellovibrio phages present among the isolates. One of the phages lysed a strain of B. bacteriovorus that requires the pres...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.10.3.516-523.1972
更新日期:1972-09-01 00:00:00
abstract::BALB/c mice infected on the scarified cornea with herpes simplex virus type 1 strain 35 [HSV-1(35)] rarely developed ocular disease even at challenge doses as high as 10(7) PFU per eye. In contrast, HSV-1(RE) consistently induced stromal keratitis at an inoculum of 2 x 10(4) PFU. The goal of this study was to determin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.5.2187-2192.1990
更新日期:1990-05-01 00:00:00
abstract::Due to increasing concerns about human infection by various H7 influenza viruses, including recent H7N9 viruses, we evaluated the genetic relationships and cross-protective efficacies of three different Eurasian H7 avian influenza viruses. Phylogenic and molecular analyses revealed that recent Eurasian H7 viruses can ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02259-16
更新日期:2017-05-12 00:00:00
abstract::The major capsid protein of polyomavirus, VP1, was separated into at least four subspecies by isoelectric focusing. One of these subspecies was selectively extracted from purified virions by mild treatment with sodium dodecyl sulfate, leaving a 140S particle enriched in the other three forms. The two most acidic subsp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.54.2.311-316.1985
更新日期:1985-05-01 00:00:00