Abstract:
:Hepatitis C virus (HCV) is a single-stranded positive-sense RNA hepatotropic virus. Despite cellular defenses, HCV is able to replicate in hepatocytes and to establish a chronic infection that could lead to severe complications and hepatocellular carcinoma. An important player in subverting the host response to HCV infection is the viral nonstructural protein NS5A, which, in addition to its role in replication and assembly, targets several pathways involved in the cellular response to viral infection. Several unbiased screens identified nucleosome assembly protein 1-like 1 (NAP1L1) as an interaction partner of HCV NS5A. Here we confirmed this interaction and mapped it to the C terminus of NS5A of both genotype 1 and 2. NS5A sequesters NAP1L1 in the cytoplasm, blocking its nuclear translocation. However, only NS5A from genotype 2 HCV, and not that from genotype 1, targets NAP1L1 for proteosome-mediated degradation. NAP1L1 is a nuclear chaperone involved in chromatin remodeling, and we demonstrated the NAP1L1-dependent regulation of specific pathways involved in cellular responses to viral infection and cell survival. Among those, we showed that lack of NAP1L1 leads to a decrease of RELA protein levels and a strong defect of IRF3 TBK1/IKKε-mediated phosphorylation, leading to inefficient RIG-I and Toll-like receptor 3 (TLR3) responses. Hence, HCV is able to modulate the host cell environment by targeting NAP1L1 through NS5A.IMPORTANCE Viruses have evolved to replicate and to overcome antiviral countermeasures of the infected cell. Hepatitis C virus is capable of establishing a lifelong chronic infection in the liver, which could develop into cirrhosis and cancer. Chronic viruses are particularly able to interfere with the cellular antiviral pathways by several different mechanisms. In this study, we identified a novel cellular target of the viral nonstructural protein NS5A and demonstrated its role in antiviral signaling. This factor, called nucleosome assembly protein 1-like 1 (NAP1L1), is a nuclear chaperone involved in the remodeling of chromatin during transcription. When it is depleted, specific signaling pathways leading to antiviral effectors are affected. Therefore, we provide evidence for both a novel strategy of virus evasion from cellular immunity and a novel role for a cellular protein, which has not been described to date.
journal_name
J Viroljournal_title
Journal of virologyauthors
Çevik RE,Cesarec M,Da Silva Filipe A,Licastro D,McLauchlan J,Marcello Adoi
10.1128/JVI.00880-17subject
Has Abstractpub_date
2017-08-24 00:00:00issue
18eissn
0022-538Xissn
1098-5514pii
JVI.00880-17journal_volume
91pub_type
杂志文章abstract::It is shown that gene 5 protein of bacteriophage M13 is one of the major proteins synthesized in vitro under the direction of M13 replicative-form DNA. By means of DNA-cellulose chromatography, this protein has been purified to homogeneity and its biological characteristics have been compared with those of its native ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.6.1466-1472.1973
更新日期:1973-12-01 00:00:00
abstract:UNLABELLED:The disease mechanisms associated with onset and secondary effects of rotavirus (RV) diarrhea remain to be determined and may not be identical. In this study, we investigated whether onset of RV diarrhea is associated with increased intestinal permeability and/or motility. To study the transit time, fluoresc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02927-13
更新日期:2014-03-01 00:00:00
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
更新日期:2006-05-01 00:00:00
abstract::The adenovirus type 2 L1 region, which is located at 30.7 to 39.2 map units on the viral genome, is transcribed from the major late promoter during both early and late stages of virus replication, and a 52,000-Mr (52K) protein-55K protein doublet has been translated in vitro on L1-specific RNA. To investigate the bios...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.57.3.839-847.1986
更新日期:1986-03-01 00:00:00
abstract::Nipah virus (NiV), of the family Paramyxoviridae, was isolated in 1999 in Malaysia from a human fatality in an outbreak of severe human encephalitis, when human infections were linked to transmission of the virus from pigs. Consequently, a swine vaccine able to abolish virus shedding is of veterinary and human health ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00263-06
更新日期:2006-08-01 00:00:00
abstract::HLA-B*52:01 is strongly associated with protection against HIV disease progression. However, the mechanisms of HLA-B*52:01-mediated immune control have not been well studied. We here describe a cohort with a majority of HIV C-clade-infected individuals from Delhi, India, where HLA-B*52:01 is highly prevalent (phenotyp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02025-19
更新日期:2020-06-16 00:00:00
abstract::The v-rel oncogene encoded by reticuloendotheliosis virus strain T is the acutely transforming member of the Rel/NF-kappaB family of transcription factors. In v-Rel-transformed cells, v-Rel exists as homodimers or heterodimers with the endogenous Rel/NF-kappaB proteins c-Rel, NF-kappaB1, NF-kappaB2, and RelA. To exami...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.10.4928-4939.2002
更新日期:2002-05-01 00:00:00
abstract::It is generally accepted that the fitness cost of resistance mutations plays a role in the persistence of transmitted drug-resistant human immunodeficiency virus type 1 and that mutations that confer a high fitness cost are less able to persist in the absence of drug pressure. Here, we show that the fitness cost of re...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02712-06
更新日期:2007-03-01 00:00:00
abstract::The yeast two-hybrid system was used to catalog all detectable interactions among the P2 nonstructural cleavage products of poliovirus type 1 (Mahoney). Evidence has been obtained for specific associations among 2A(pro), 2BC, 2C, and 2B. Specifically, 2A(pro) can interact with itself and 2BC and its cleavage products ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.2.1297-1307.1998
更新日期:1998-02-01 00:00:00
abstract::Epstein-Barr virus (EBV)-encoded molecules have been detected in the tumor tissues of several cancers, including nasopharyngeal carcinoma (NPC), suggesting that EBV plays an important role in tumorigenesis. However, the nature of EBV with respect to genome width in vivo and whether EBV undergoes clonal expansion in th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00823-11
更新日期:2011-11-01 00:00:00
abstract::Spleen cells from mice, 4 to 60 days after infection with mouse hepatitis virus type 4, produced interleukin-2, as well as interleukin-3, in the absence of exogenous stimulants in vitro. This unique lymphokine production by mouse hepatitis virus type 4 infection was controlled by host genes. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.9.3506-3508.1988
更新日期:1988-09-01 00:00:00
abstract::The active site serine of the acetylesterase of influenza C virus was localized to amino acid 71 of the hemagglutinin-esterase protein by affinity labeling with 3H-labeled diisopropylfluorophosphate. This serine and the adjacent amino acids (Phe-Gly-Asp-Ser) are part of a consensus sequence motif found in serine hydro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.5.2056-2062.1989
更新日期:1989-05-01 00:00:00
abstract::Initiation of the Epstein-Barr virus (EBV) lytic cycle is dependent on expression of the viral transactivator Zta, which is encoded by the BZLF1 gene. Described here is an initial mapping of the regions of Zta involved in activating transcription. The data indicate that the amino-terminal 153 amino acids of Zta are im...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.2.922-929.1992
更新日期:1992-02-01 00:00:00
abstract::The rapid and accurate identification of pathogens is critical in the control of infectious disease. To this end, we analyzed the capacity for viral detection and identification of a newly described high-density resequencing microarray (RMA), termed PathogenID, which was designed for multiple pathogen detection using ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00771-10
更新日期:2010-09-01 00:00:00
abstract::Members of the tripartite interaction motif (TRIM) family of E3 ligases are emerging as critical regulators of innate immunity. To identify new regulators, we carried out a screen of 43 human TRIM proteins for the ability to activate NF-κB, AP-1, and interferon, hallmarks of many innate immune signaling pathways. We i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01804-12
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.63.5.2411-2414.1989
更新日期:1989-05-01 00:00:00
abstract::Most patients infected with hepatitis C virus (HCV) become chronic carriers. Viruses that efficiently establish persistent infections must have effective ways of evading host defenses. In the case of HCV, little is known about how chronic infections are established or maintained. Besides hepatocytes, several reports s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.2.772-781.2001
更新日期:2001-01-01 00:00:00
abstract::Three hypervariable regions were identified in a central portion of open reading frame 1 of TT virus DNA, which codes for a putative capsid protein of 770 amino acids. TT virus circulates as quasispecies, with many amino acid substitutions in hypervariable regions, to evade immune surveillance of the hosts and to esta...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.11.9604-9608.1999
更新日期:1999-11-01 00:00:00
abstract::Profiles of bacteriophage T4 early proteins resolved by a two-dimensional nonequilibrium pH gradient electrophoresis system (P. Z. O'Farrell, H. M. Goodman, and P. H. O'Farrell, Cell 12:1133--1142, 1977) are presented. Over 65 phage-induced proteins were resolved. Amber or deletion mutants were used to identify 17 pro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.42.3.767-772.1982
更新日期:1982-06-01 00:00:00
abstract::APOBEC3G (APO3G) is a cytidine deaminase that restricts replication of vif-defective human immunodeficiency virus type 1 (HIV-1). Like other members of the cellular deaminase family, APO3G has the propensity to form homo-multimers. In the current study, we investigated the functional determinants for multimerization o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.10.4673-4682.2006
更新日期:2006-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.3.625-631.1973
更新日期:1973-09-01 00:00:00
abstract::The full-length genome of human cytomegalovirus strain AD169 was cloned as an infectious bacterial artificial chromosome (BAC) plasmid, pAD/Cre. The BAC vector, flanked by LoxP sites, was inserted immediately after the Us28 open reading frame without deletion of any viral sequences. The BAC vector contained the Cre re...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.5.2316-2328.2002
更新日期:2002-03-01 00:00:00
abstract::The regulatory proteins Nef, Rev, and Tat of human immunodeficiency virus type 1 (HIV-1) are attractive targets for vaccine development, since induction of effective immune responses targeting these early proteins may best control virus replication. Here we investigated whether vaccination with biologically active Tat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.8.3800-3809.2002
更新日期:2002-04-01 00:00:00
abstract::Induction of apoptotic cell death generally requires the participation of cysteine proteases belonging to the caspase family. However, and similar to most cell types, mouse fibroblasts are normally resistant to tumor necrosis factor alpha (TNF-alpha)-induced apoptosis. Surprisingly, TNF-alpha treatment of vaccinia vir...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.16.7470-7477.2000
更新日期:2000-08-01 00:00:00
abstract::Previous studies have suggested that coxsackievirus B (CVB) activates CD8(+) T cells in vivo, but the extent of this activation and the antigen specificity of the CD8(+) T cells remain uncertain. Furthermore, CVB-induced CD4(+) T-cell responses have not been carefully investigated. Herein, we evaluate CD8(+) and CD4(+...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02639-07
更新日期:2008-05-01 00:00:00
abstract::The parameters governing the activity of the cloned T4 gene 23, which codes for the major T4 head protein, were analyzed. Suppressor-negative bacteria carrying wild-type T4 gene 23 cloned into plasmid pCR1 or pBR322 were infected with T4 gene 23 amber phage also carrying mutations in the following genes: (i) denA and ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.39.1.46-59.1981
更新日期:1981-07-01 00:00:00
abstract::Viruses with spindle-shaped virions are abundant in diverse environments. Over the years, such viruses have been isolated from a wide range of archaeal hosts. Evolutionary relationships between them remained enigmatic, however. Here, using structural proteins as markers, we define familial ties among these "dark horse...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02941-13
更新日期:2014-02-01 00:00:00
abstract::Immunogenic regions of the gp41 transmembrane protein of human immunodeficiency virus type 1 (HIV-1) were previously mapped by examining polyclonal sera from HIV-infected patients and rodent polyclonal and monoclonal antibodies (MAbs) to peptides of gp41. To define the epitopes within these regions to which infected h...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.9.4832-4838.1991
更新日期:1991-09-01 00:00:00
abstract::Adenovirus type 19 is a major cause of epidemic keratoconjunctivitis, the only ocular adenoviral infection associated with prolonged corneal inflammation. In this study, we investigated the role of phosphoinositide 3-kinase (PI3K) and Akt and their downstream targets in adenovirus infection, and here we report the nov...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.19.12332-12341.2005
更新日期:2005-10-01 00:00:00
abstract::Despite reports of viral genetic defects in persons who control human immunodeficiency virus type 1 (HIV-1) in the absence of antiviral therapy, the extent to which such defects contribute to the long-term containment of viremia is not known. Most previous studies examining for such defects have involved small numbers...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00535-08
更新日期:2008-09-01 00:00:00