Evidence that the human cytomegalovirus IE2-86 protein binds mdm2 and facilitates mdm2 degradation.

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, targeting p53 for proteasomal degradation. Here we report that, in contrast to uninfected cells, mdm2 was undetectable upon treatment of infected fibroblasts with the proteasome inhibitor MG132. Cellular depletion of mdm2 was reproducible in p53-null cells transfected with the HCMV IE2-86 protein, but not with IE172, independently of the endogenous mdm2 promoter. IE2-86 also prevented the emergence of presumably ubiquitinated species of p53. The regions of IE2-86 important for mdm2 depletion were those containing the sequences corresponding to the putative zinc finger and C-terminal acidic motifs. mdm2 and IE2-86 coimmunoprecipitated in transfected and infected cell lysates and in a cell-free system. IE2-86 blocked mdm2's p53-independent transactivation of the cyclin A promoter in transient-transfection experiments. Pulse-chase experiments revealed that IE2-86 but not IE1-72 or several loss-of-function IE2-86 mutants increased the half-life of p53 and reduced the half-life of mdm2. Short interfering RNA-mediated depletion of IE2-86 restored the ability of HCMV-infected cells to accumulate mdm2 in response to proteasome inhibition. Taken together, the data suggest that specific interactions between IE2-86 and mdm2 cause proteasome-independent degradation of mdm2 and that this may be important for the accumulation of p53 in HCMV-infected cells.

journal_name

J Virol

journal_title

Journal of virology

authors

Zhang Z,Evers DL,McCarville JF,Dantonel JC,Huong SM,Huang ES

doi

10.1128/JVI.80.8.3833-3843.2006

subject

Has Abstract

pub_date

2006-04-01 00:00:00

pages

3833-43

issue

8

eissn

0022-538X

issn

1098-5514

pii

80/8/3833

journal_volume

80

pub_type

杂志文章
  • Interaction of JC virus agno protein with T antigen modulates transcription and replication of the viral genome in glial cells.

    abstract::In addition to encoding the structural and regulatory proteins, many viruses encode auxiliary proteins, some of which have been shown to play important roles in lytic and latent states of the viruses. The human neurotropic JC virus (JCV) genome encodes an auxiliary protein called Agno whose function remains unknown. H...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.75.3.1476-1486.2001

    authors: Safak M,Barrucco R,Darbinyan A,Okada Y,Nagashima K,Khalili K

    更新日期:2001-02-01 00:00:00

  • Mutual interference between genomic RNA replication and subgenomic mRNA transcription in brome mosaic virus.

    abstract::Replication by many positive-strand RNA viruses includes genomic RNA amplification and subgenomic mRNA (sgRNA) transcription. For brome mosaic virus (BMV), both processes occur in virus-induced, membrane-associated compartments, require BMV replication factors 1a and 2a, and use negative-strand RNA3 as a template for ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.79.3.1438-1451.2005

    authors: Grdzelishvili VZ,Garcia-Ruiz H,Watanabe T,Ahlquist P

    更新日期:2005-02-01 00:00:00

  • Structural stability of influenza A(H1N1)pdm09 virus hemagglutinins.

    abstract:UNLABELLED:The noncovalent interactions that mediate trimerization of the influenza hemagglutinin (HA) are important determinants of its biological activities. Recent studies have demonstrated that mutations in the HA trimer interface affect the thermal and pH sensitivities of HA, suggesting a possible impact on vaccin...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02278-13

    authors: Yang H,Chang JC,Guo Z,Carney PJ,Shore DA,Donis RO,Cox NJ,Villanueva JM,Klimov AI,Stevens J

    更新日期:2014-05-01 00:00:00

  • Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2.

    abstract::Infection of receptor-bearing cells by coronaviruses is mediated by their spike (S) proteins. The coronavirus (SARS-CoV) that causes severe acute respiratory syndrome (SARS) infects cells expressing the receptor angiotensin-converting enzyme 2 (ACE2). Here we show that codon optimization of the SARS-CoV S-protein gene...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.78.19.10628-10635.2004

    authors: Moore MJ,Dorfman T,Li W,Wong SK,Li Y,Kuhn JH,Coderre J,Vasilieva N,Han Z,Greenough TC,Farzan M,Choe H

    更新日期:2004-10-01 00:00:00

  • Irreversible conversion of the physical state of herpes simplex virus preceding inactivation by thermal or antibody treatment.

    abstract::The buoyant density characteristics of infectious particles of herpes simplex virus types 1 and 2 were studied by centrifugation in sucrose and cesium chloride density gradients with a high resolution and satisfactory infectivity recovery. It was shown that two populations of infectious virions differing in buoyant de...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.38.2.737-748.1981

    authors: Yanagi K

    更新日期:1981-05-01 00:00:00

  • Human rhinovirus 2 induces the autophagic pathway and replicates more efficiently in autophagic cells.

    abstract::Picornaviruses rearrange cellular membranes to form cytosolic replication sites. In the case of poliovirus and several other picornaviruses, these membranes are derived from subversion of the cellular autophagy pathway. We also reported observation of autophagosome-like structures during infection by two human rhinovi...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00316-11

    authors: Klein KA,Jackson WT

    更新日期:2011-09-01 00:00:00

  • The Mlvi-1 locus involved in the induction of rat T-cell lymphomas and the pvt-1/Mis-1 locus are identical.

    abstract::Mlvi-1 defines a locus of proviral integration in rat thymomas induced by Moloney murine leukemia virus. pvt-1/Mis-1 represents an independently identified locus which becomes rearranged either by chromosomal translocation in murine plasmacytomas or by provirus insertion in retrovirus-induced murine and rat thymic lym...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.63.5.2366-2369.1989

    authors: Koehne CF,Lazo PA,Alves K,Lee JS,Tsichlis PN,O'Donnell PV

    更新日期:1989-05-01 00:00:00

  • Identification of an internal ribosome entry segment in the 5' region of the mouse VL30 retrotransposon and its use in the development of retroviral vectors.

    abstract::Mouse virus-like 30S RNAs (VL30m) constitute a family of retrotransposons, present at 100 to 200 copies, dispersed in the mouse genome. They display little sequence homology to Moloney murine leukemia virus (MoMLV), do not encode virus-like proteins, and have not been implicated in retroviral carcinogenesis. However, ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.73.10.8393-8402.1999

    authors: López-Lastra M,Ulrici S,Gabus C,Darlix JL

    更新日期:1999-10-01 00:00:00

  • Complete nucleotide sequence of simian endogenous type D retrovirus with intact genome organization: evidence for ancestry to simian retrovirus and baboon endogenous virus.

    abstract::A complete endogenous type D viral genome has been isolated from a baboon genomic library. The provirus, simian endogenous retrovirus (SERV), is 8,393 nucleotides long and contains two long terminal repeats and complete genes for gag, pro, pol, and env. The primer binding site is complementary to tRNA(Lys)3, like in l...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.71.5.3666-3676.1997

    authors: van der Kuyl AC,Mang R,Dekker JT,Goudsmit J

    更新日期:1997-05-01 00:00:00

  • Orsay δ Protein Is Required for Nonlytic Viral Egress.

    abstract::Nonenveloped gastrointestinal viruses, such as human rotavirus, can exit infected cells from the apical surface without cell lysis. The mechanism of such nonlytic exit is poorly understood. The nonenveloped Orsay virus is an RNA virus infecting the intestine cells of the nematode Caenorhabditis elegans Dye staining re...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00745-18

    authors: Yuan W,Zhou Y,Fan Y,Tao YJ,Zhong W

    更新日期:2018-06-29 00:00:00

  • A single regulatory region modulates both cis activation and trans activation of the herpes simplex virus VP5 promoter in transient-expression assays in vivo.

    abstract::A detailed analysis of the expression of the bacterial chloramphenicol acetyltransferase gene controlled by the herpes simplex virus major capsid protein (VP5) promoter showed that this promoter can be functionally separated into an 80-base core region, which has the minimal information required to serve as a pol II p...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.60.2.460-469.1986

    authors: Blair ED,Wagner EK

    更新日期:1986-11-01 00:00:00

  • Plasticity of Amino Acid Residue 145 Near the Receptor Binding Site of H3 Swine Influenza A Viruses and Its Impact on Receptor Binding and Antibody Recognition.

    abstract::The hemagglutinin (HA), a glycoprotein on the surface of influenza A virus (IAV), initiates the virus life cycle by binding to terminal sialic acid (SA) residues on host cells. The HA gradually accumulates amino acid substitutions that allow IAV to escape immunity through a mechanism known as antigenic drift. We recen...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01413-18

    authors: Santos JJS,Abente EJ,Obadan AO,Thompson AJ,Ferreri L,Geiger G,Gonzalez-Reiche AS,Lewis NS,Burke DF,Rajão DS,Paulson JC,Vincent AL,Perez DR

    更新日期:2019-01-04 00:00:00

  • Studies of an influenza A virus temperature-sensitive mutant identify a late role for NP in the formation of infectious virions.

    abstract::The influenza A virus nucleoprotein (NP) is a single-stranded RNA-binding protein that encapsidates the virus genome and has essential functions in viral-RNA synthesis. Here, we report the characterization of a temperature-sensitive (ts) NP mutant (US3) originally generated in fowl plague virus (A/chicken/Rostock/34)....

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01424-08

    authors: Noton SL,Simpson-Holley M,Medcalf E,Wise HM,Hutchinson EC,McCauley JW,Digard P

    更新日期:2009-01-01 00:00:00

  • Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein.

    abstract::A detailed kinetic and quantitative analysis of the early and late biosynthetic events undergone by the human immunodeficiency virus type 1 envelope protein expressed by a recombinant vaccinia virus was performed. Early folding events that occurred in the endoplasmic reticulum included disulfide bond formation (t1/2 a...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.65.4.2047-2055.1991

    authors: Earl PL,Moss B,Doms RW

    更新日期:1991-04-01 00:00:00

  • Reversion of Q beta RNA phage mutants by homologous RNA recombination.

    abstract::Q beta phage RNAs with inactivating insertion (8-base) or deletion (17-base) mutations within their replicase genes were prepared from modified Q beta cDNAs and transfected into Escherichia coli spheroplasts containing Q beta replicase provided in trans by a resident plasmid. Replicase-defective (Rep-) Q beta phage pr...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.66.4.2435-2442.1992

    authors: Palasingam K,Shaklee PN

    更新日期:1992-04-01 00:00:00

  • Functional characterization of the genomic promoter of borna disease virus (BDV): implications of 3'-terminal sequence heterogeneity for BDV persistence.

    abstract::Borna disease virus (BDV) is an enveloped virus with a genome organization characteristic of Mononegavirales. However, based on its unique features, BDV is considered the prototypic member of a new virus family, Bornaviridae, within the order Mononegavirales. We have described the establishment of a reverse genetics s...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.79.10.6544-6550.2005

    authors: Rosario D,Perez M,de la Torre JC

    更新日期:2005-05-01 00:00:00

  • Fusion formation by the uncleaved spike protein of murine coronavirus JHMV variant cl-2.

    abstract::The fusogenic properties of the uncleaved spike (S) protein of murine coronavirus JHMV variant cl-2 were studied by expressing the S protein with a deleted putative cleavage site. The amino acid sequence of the putative cleavage site, Arg-Arg-Ala-Arg-Arg, was replaced by Arg-Thr-Ala-Leu-Glu by in vitro mutagenesis of ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.67.3.1195-1202.1993

    authors: Taguchi F

    更新日期:1993-03-01 00:00:00

  • Human adenovirus type 9-induced rat mammary tumors.

    abstract::Following subcutaneous inoculation of newborn Wistar-Furth rats with human adenovirus type 9 (Ad9), 16 of 16 female and 0 of 11 male rats developed mammary tumors. Tumor-positive animals usually developed tumors in multiple glands. Histopathological analyses indicated that three general categories of tumor could be id...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.65.6.3192-3202.1991

    authors: Javier R,Raska K Jr,Macdonald GJ,Shenk T

    更新日期:1991-06-01 00:00:00

  • Herpes simplex virus type 1 DNA-packaging protein UL17 is required for efficient binding of UL25 to capsids.

    abstract::Herpes simplex virus type 1 packages its DNA genome into a precursor capsid, referred to as the procapsid. Of the three capsid-associated DNA-packaging proteins, UL17, UL25, and UL6, only UL17 and UL6 appear to be components of the procapsid, with UL25 being added subsequently. To determine whether the association of ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.80.5.2118-2126.2006

    authors: Thurlow JK,Murphy M,Stow ND,Preston VG

    更新日期:2006-03-01 00:00:00

  • Identification of paramyxovirus V protein residues essential for STAT protein degradation and promotion of virus replication.

    abstract::Some paramyxovirus V proteins induce STAT protein degradation, and the amino acids essential for this process in the human parainfluenza virus type 2 (hPIV2) V protein have been studied. Various recombinant hPIV2s and cell lines constitutively expressing various mutant V proteins were generated. We found that V protei...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.79.13.8591-8601.2005

    authors: Nishio M,Tsurudome M,Ito M,Garcin D,Kolakofsky D,Ito Y

    更新日期:2005-07-01 00:00:00

  • Characterization of lymphocytic choriomeningitis virus-binding protein(s): a candidate cellular receptor for the virus.

    abstract::The attachment of lymphocytic choriomeningitis virus (LCMV) to murine and primate cell lines was quantitated by a fluorescence-activated cell sorter assay in which binding of biotinylated virus was detected with streptavidin-fluorescein isothiocyanate. Cell lines that were readily infected by LCMV (e.g., MC57, Rin, BH...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.66.12.7270-7281.1992

    authors: Borrow P,Oldstone MB

    更新日期:1992-12-01 00:00:00

  • Human immunodeficiency virus type 1 (HIV-1)-specific CD4+ T cells that proliferate in vitro detected in samples from most viremic subjects and inversely associated with plasma HIV-1 levels.

    abstract::Diminished in vitro proliferation of human immunodeficiency virus type 1 (HIV-1)-specific CD4+T cells has been associated with HIV-1 viremia and declining CD4+ T-cell counts during chronic infection. To better understand this phenomenon, we examined whether HIV-1 Gag p24 antigen-induced CD4+ T-cell proliferation might...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.78.22.12638-12646.2004

    authors: Boritz E,Palmer BE,Wilson CC

    更新日期:2004-11-01 00:00:00

  • Protease digestion of hepatitis A virus: disparate effects on capsid proteins, antigenicity, and infectivity.

    abstract::High concentrations of either trypsin or chymotrypsin caused nearly complete cleavage of capsid protein VP2 of hepatitis A virus but did not significantly reduce the infectivity, thermostability, or antigenicity of the virus. Chymotrypsin also had a lesser effect on VP1. These findings indicate the presence of a prote...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.65.10.5636-5640.1991

    authors: Lemon SM,Amphlett E,Sangar D

    更新日期:1991-10-01 00:00:00

  • Fluorescent tagging of herpes simplex virus tegument protein VP13/14 in virus infection.

    abstract::The cellular site of herpesvirus tegument assembly has yet to be defined. We have previously used a recombinant herpes simplex virus type 1 expressing a green fluorescent protein (GFP)-tagged tegument protein, namely VP22, to show that VP22 is localized exclusively to the cytoplasm during infection. Here we have const...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.75.6.2575-2583.2001

    authors: Donnelly M,Elliott G

    更新日期:2001-03-01 00:00:00

  • Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Inhibits Major Histocompatibility Complex Class II Expression by Disrupting Enhanceosome Assembly through Binding with the Regulatory Factor X Complex.

    abstract:UNLABELLED:Major histocompatibility complex class II (MHC-II) molecules play a central role in adaptive antiviral immunity by presenting viral peptides to CD4(+) T cells. Due to their key role in adaptive immunity, many viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), have evolved multiple strategies ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.03713-14

    authors: Thakker S,Purushothaman P,Gupta N,Challa S,Cai Q,Verma SC

    更新日期:2015-05-01 00:00:00

  • Constitutive expression of an ISGF2/IRF1 transgene leads to interferon-independent activation of interferon-inducible genes and resistance to virus infection.

    abstract::Interferon (IFN)-stimulated gene factor 2 (ISGF2) plays a role in transcription of the beta IFN (IFN-beta) gene and IFN-stimulated genes (ISGs) and may function as a central mediator of cytokine responses. Constitutive ISGF2 transgene expression resulted in substantial resistance to three RNA virus families. This phen...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.66.7.4470-4478.1992

    authors: Pine R

    更新日期:1992-07-01 00:00:00

  • The glycosylation status of PrPC is a key factor in determining transmissible spongiform encephalopathy transmission between species.

    abstract:UNLABELLED:The risk of transmission of transmissible spongiform encephalopathies (TSE) between different species has been notoriously unpredictable because the mechanisms of transmission are not fully understood. A transmission barrier between species often prevents infection of a new host with a TSE agent. Nonetheless...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02296-14

    authors: Wiseman FK,Cancellotti E,Piccardo P,Iremonger K,Boyle A,Brown D,Ironside JW,Manson JC,Diack AB

    更新日期:2015-05-01 00:00:00

  • Variable constraints on the principal immunodominant domain of the transmembrane glycoprotein of human immunodeficiency virus type 1.

    abstract::Lentiviruses have in their transmembrane glycoprotein (TM) a highly immunogenic structure referred to as the principal immunodominant domain (PID). The PID forms a loop of 5 to 7 amino acids between two conserved cysteines. Previous studies showed that envelope (Env) glycoprotein functions of feline immunodeficiency v...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.73.7.5698-5706.1999

    authors: Merat R,Raoul H,Leste-Lasserre T,Sonigo P,Pancino G

    更新日期:1999-07-01 00:00:00

  • An element in the bovine papillomavirus late 3' untranslated region reduces polyadenylated cytoplasmic RNA levels.

    abstract::Expression of the two bovine papillomavirus type 1 (BPV-1) late genes, L1 and L2, coding for the two capsid proteins, is limited to terminally differentiated keratinocytes in bovine fibropapillomas. This pattern of expression is determined both by the activity of the late promoter and by the inhibition of late region ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.65.11.5806-5812.1991

    authors: Furth PA,Baker CC

    更新日期:1991-11-01 00:00:00

  • Mapping of sequences in Pseudorabies virus pUL34 that are required for formation and function of the nuclear egress complex.

    abstract::The nuclear egress complex (NEC) is required for efficient translocation of newly synthesized herpesvirus nucleocapsids from the nucleus to the cytosol. It consists of the type II membrane protein pUL34 which interacts with pUL31 at the inner nuclear membrane (INM). To map regions within pUL34 required for nuclear mem...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00021-13

    authors: Paßvogel L,Trübe P,Schuster F,Klupp BG,Mettenleiter TC

    更新日期:2013-04-01 00:00:00