Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral host defense against varicella-zoster virus.

Abstract:

:The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs, as shown in cells infected in vitro, but information about the fate of PML-NBs and their functions in herpesvirus infected cells in vivo is limited. Varicella-zoster virus (VZV) is an alphaherpesvirus with tropism for skin, lymphocytes and sensory ganglia, where it establishes latency. Here, we identify large PML-NBs that sequester newly assembled nucleocapsids (NC) in neurons and satellite cells of human dorsal root ganglia (DRG) and skin cells infected with VZV in vivo. Quantitative immuno-electron microscopy revealed that these distinctive nuclear bodies consisted of PML fibers forming spherical cages that enclosed mature and immature VZV NCs. Of six PML isoforms, only PML IV promoted the sequestration of NCs. PML IV significantly inhibited viral infection and interacted with the ORF23 capsid surface protein, which was identified as a target for PML-mediated NC sequestration. The unique PML IV C-terminal domain was required for both capsid entrapment and antiviral activity. Similar large PML-NBs, termed clastosomes, sequester aberrant polyglutamine (polyQ) proteins, such as Huntingtin (Htt), in several neurodegenerative disorders. We found that PML IV cages co-sequester HttQ72 and ORF23 protein in VZV infected cells. Our data show that PML cages contribute to the intrinsic antiviral defense by sensing and entrapping VZV nucleocapsids, thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The efficient sequestration of virion capsids in PML cages appears to be the outcome of a basic cytoprotective function of this distinctive category of PML-NBs in sensing and safely containing nuclear aggregates of aberrant proteins.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Reichelt M,Wang L,Sommer M,Perrino J,Nour AM,Sen N,Baiker A,Zerboni L,Arvin AM

doi

10.1371/journal.ppat.1001266

subject

Has Abstract

pub_date

2011-02-03 00:00:00

pages

e1001266

issue

2

eissn

1553-7366

issn

1553-7374

journal_volume

7

pub_type

杂志文章
  • Towards a structural comprehension of bacterial type VI secretion systems: characterization of the TssJ-TssM complex of an Escherichia coli pathovar.

    abstract::Type VI secretion systems (T6SS) are trans-envelope machines dedicated to the secretion of virulence factors into eukaryotic or prokaryotic cells, therefore required for pathogenesis and/or for competition towards neighboring bacteria. The T6SS apparatus resembles the injection device of bacteriophage T4, and is ancho...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002386

    authors: Felisberto-Rodrigues C,Durand E,Aschtgen MS,Blangy S,Ortiz-Lombardia M,Douzi B,Cambillau C,Cascales E

    更新日期:2011-11-01 00:00:00

  • Rapid perturbation in viremia levels drives increases in functional avidity of HIV-specific CD8 T cells.

    abstract::The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood. We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection (PHI) or chronic (progressive and non-progressive) infection. The funct...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003423

    authors: Viganò S,Bellutti Enders F,Miconnet I,Cellerai C,Savoye AL,Rozot V,Perreau M,Faouzi M,Ohmiti K,Cavassini M,Bart PA,Pantaleo G,Harari A

    更新日期:2013-01-01 00:00:00

  • Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2.

    abstract::Tetherin, also known as BST2, CD317 or HM1.24, was recently identified as an interferon-inducible host-cell factor that interferes with the detachment of virus particles from infected cells. HIV-1 overcomes this restriction by expressing an accessory protein, Vpu, which counteracts tetherin. Since lentiviruses of the ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000429

    authors: Jia B,Serra-Moreno R,Neidermyer W,Rahmberg A,Mackey J,Fofana IB,Johnson WE,Westmoreland S,Evans DT

    更新日期:2009-05-01 00:00:00

  • AIG1 affects in vitro and in vivo virulence in clinical isolates of Entamoeba histolytica.

    abstract::The disease state of amebiasis, caused by Entamoeba histolytica, varies from asymptomatic to severe manifestations that include dysentery and extraintestinal abscesses. The virulence factors of the pathogen, and host defense mechanisms, contribute to the outcomes of infection; however, the underlying genetic factors, ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006882

    authors: Nakada-Tsukui K,Sekizuka T,Sato-Ebine E,Escueta-de Cadiz A,Ji DD,Tomii K,Kuroda M,Nozaki T

    更新日期:2018-03-19 00:00:00

  • Two-component signal transduction system CBO0787/CBO0786 represses transcription from botulinum neurotoxin promoters in Clostridium botulinum ATCC 3502.

    abstract::Blocking neurotransmission, botulinum neurotoxin is the most poisonous biological substance known to mankind. Despite its infamy as the scourge of the food industry, the neurotoxin is increasingly used as a pharmaceutical to treat an expanding range of muscle disorders. Whilst neurotoxin expression by the spore-formin...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003252

    authors: Zhang Z,Korkeala H,Dahlsten E,Sahala E,Heap JT,Minton NP,Lindström M

    更新日期:2013-03-01 00:00:00

  • Human APOBEC3 induced mutation of human immunodeficiency virus type-1 contributes to adaptation and evolution in natural infection.

    abstract::Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A) mutagenes...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004281

    authors: Kim EY,Lorenzo-Redondo R,Little SJ,Chung YS,Phalora PK,Maljkovic Berry I,Archer J,Penugonda S,Fischer W,Richman DD,Bhattacharya T,Malim MH,Wolinsky SM

    更新日期:2014-07-31 00:00:00

  • Correction: Alternate splicing of transcripts shape macrophage response to Mycobacterium tuberculosis infection.

    abstract::[This corrects the article DOI: 10.1371/journal.ppat.1006236.]. ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章,已发布勘误

    doi:10.1371/journal.ppat.1006833

    authors: Kalam H,Fontana MF,Kumar D

    更新日期:2018-01-04 00:00:00

  • The respiratory syncytial virus polymerase has multiple RNA synthesis activities at the promoter.

    abstract::Respiratory syncytial virus (RSV) is an RNA virus in the Family Paramyxoviridae. Here, the activities performed by the RSV polymerase when it encounters the viral antigenomic promoter were examined. RSV RNA synthesis was reconstituted in vitro using recombinant, isolated polymerase and an RNA oligonucleotide template ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002980

    authors: Noton SL,Deflubé LR,Tremaglio CZ,Fearns R

    更新日期:2012-01-01 00:00:00

  • Reprogramming the unfolded protein response for replication by porcine reproductive and respiratory syndrome virus.

    abstract::The unfolded protein response (UPR) in the endoplasmic reticulum (ER) constitutes a critical component of host innate immunity against microbial infections. In this report, we show that porcine reproductive and respiratory syndrome virus (PRRSV) utilizes the UPR machinery for its own benefit. We provide evidence that ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008169

    authors: Gao P,Chai Y,Song J,Liu T,Chen P,Zhou L,Ge X,Guo X,Han J,Yang H

    更新日期:2019-11-18 00:00:00

  • An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.

    abstract::Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candida...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004875

    authors: de Macêdo JP,Schumann Burkard G,Niemann M,Barrett MP,Vial H,Mäser P,Roditi I,Schneider A,Bütikofer P

    更新日期:2015-05-06 00:00:00

  • RIG-I and MDA-5 detection of viral RNA-dependent RNA polymerase activity restricts positive-strand RNA virus replication.

    abstract::Type I interferons (IFN) are important for antiviral responses. Melanoma differentiation-associated gene 5 (MDA-5) and retinoic acid-induced gene I (RIG-I) proteins detect cytosolic double-stranded RNA (dsRNA) or 5'-triphosphate (5'-ppp) RNA and mediate IFN production. Cytosolic 5'-ppp RNA and dsRNA are generated duri...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003610

    authors: Nikonov A,Mölder T,Sikut R,Kiiver K,Männik A,Toots U,Lulla A,Lulla V,Utt A,Merits A,Ustav M

    更新日期:2013-01-01 00:00:00

  • TREM-1 deficiency can attenuate disease severity without affecting pathogen clearance.

    abstract::Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune reactions. While TREM-1-amplified responses likely aid an improved detection and elimination of pathogens, excessive production of cytokines and oxygen radicals can also severely harm the host. Studies add...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003900

    authors: Weber B,Schuster S,Zysset D,Rihs S,Dickgreber N,Schürch C,Riether C,Siegrist M,Schneider C,Pawelski H,Gurzeler U,Ziltener P,Genitsch V,Tacchini-Cottier F,Ochsenbein A,Hofstetter W,Kopf M,Kaufmann T,Oxenius A,Reith W

    更新日期:2014-01-01 00:00:00

  • Analysis of the SUMO2 Proteome during HSV-1 Infection.

    abstract::Covalent linkage to members of the small ubiquitin-like (SUMO) family of proteins is an important mechanism by which the functions of many cellular proteins are regulated. Sumoylation has roles in the control of protein stability, activity and localization, and is involved in the regulation of transcription, gene expr...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005059

    authors: Sloan E,Tatham MH,Groslambert M,Glass M,Orr A,Hay RT,Everett RD

    更新日期:2015-07-22 00:00:00

  • A freeze frame view of vesicular stomatitis virus transcription defines a minimal length of RNA for 5' processing.

    abstract::The RNA synthesis machinery of vesicular stomatitis virus (VSV) comprises the genomic RNA encapsidated by the viral nucleocapsid protein (N) and associated with the RNA dependent RNA polymerase, the viral components of which are a large protein (L) and an accessory phosphoprotein (P). The 241 kDa L protein contains al...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002073

    authors: Tekes G,Rahmeh AA,Whelan SP

    更新日期:2011-06-01 00:00:00

  • acr-23 Encodes a monepantel-sensitive channel in Caenorhabditis elegans.

    abstract::Monepantel is a member of the recently identified class of anthelmintics known as the amino-acetonitrile derivatives (AADs). Monepantel controls all major gastro-intestinal nematodes in sheep including those that are resistant to the classical anthelmintics. Previous studies have shown that the Caenorhabditis elegans ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003524

    authors: Rufener L,Bedoni N,Baur R,Rey S,Glauser DA,Bouvier J,Beech R,Sigel E,Puoti A

    更新日期:2013-01-01 00:00:00

  • Mechanism of genomic instability in cells infected with the high-risk human papillomaviruses.

    abstract::In HPV-related cancers, the "high-risk" human papillomaviruses (HPVs) are frequently found integrated into the cellular genome. The integrated subgenomic HPV fragments express viral oncoproteins and carry an origin of DNA replication that is capable of initiating bidirectional DNA re-replication in the presence of HPV...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000397

    authors: Kadaja M,Isok-Paas H,Laos T,Ustav E,Ustav M

    更新日期:2009-04-01 00:00:00

  • A novel phase variation mechanism in the meningococcus driven by a ligand-responsive repressor and differential spacing of distal promoter elements.

    abstract::Phase variable expression, mediated by high frequency reversible changes in the length of simple sequence repeats, facilitates adaptation of bacterial populations to changing environments and is frequently important in bacterial virulence. Here we elucidate a novel phase variable mechanism for NadA, an adhesin and inv...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000710

    authors: Metruccio MM,Pigozzi E,Roncarati D,Berlanda Scorza F,Norais N,Hill SA,Scarlato V,Delany I

    更新日期:2009-12-01 00:00:00

  • Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils.

    abstract::In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000362

    authors: Rittner HL,Hackel D,Voigt P,Mousa S,Stolz A,Labuz D,Schäfer M,Schaefer M,Stein C,Brack A

    更新日期:2009-04-01 00:00:00

  • Antibody evasion by a gammaherpesvirus O-glycan shield.

    abstract::All gammaherpesviruses encode a major glycoprotein homologous to the Epstein-Barr virus gp350. These glycoproteins are often involved in cell binding, and some provide neutralization targets. However, the capacity of gammaherpesviruses for long-term transmission from immune hosts implies that in vivo neutralization is...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002387

    authors: Machiels B,Lété C,Guillaume A,Mast J,Stevenson PG,Vanderplasschen A,Gillet L

    更新日期:2011-11-01 00:00:00

  • The AraC Negative Regulator family modulates the activity of histone-like proteins in pathogenic bacteria.

    abstract::The AraC Negative Regulators (ANR) comprise a large family of virulence regulators distributed among diverse clinically important Gram-negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., and pathogenic E. coli strains. We have previously reported broad effects of...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006545

    authors: Santiago AE,Yan MB,Hazen TH,Sauder B,Meza-Segura M,Rasko DA,Kendall MM,Ruiz-Perez F,Nataro JP

    更新日期:2017-08-14 00:00:00

  • The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein.

    abstract::PB1-F2 is a 90 amino acid protein that is expressed from the +1 open reading frame in the PB1 gene of some influenza A viruses and has been shown to contribute to viral pathogenicity. Notably, a serine at position 66 (66S) in PB1-F2 is known to increase virulence compared to an isogenic virus with an asparagine (66N) ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002067

    authors: Varga ZT,Ramos I,Hai R,Schmolke M,García-Sastre A,Fernandez-Sesma A,Palese P

    更新日期:2011-06-01 00:00:00

  • Maternal schistosomiasis impairs offspring Interleukin-4 production and B cell expansion.

    abstract::Epidemiological studies have identified a correlation between maternal helminth infections and reduced immunity to some early childhood vaccinations, but the cellular basis for this is poorly understood. Here, we investigated the effects of maternal Schistosoma mansoni infection on steady-state offspring immunity, as ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1009260

    authors: Cortés-Selva D,Gibbs L,Ready A,Ekiz HA,O'Connell R,Rajwa B,Fairfax KC

    更新日期:2021-02-01 00:00:00

  • H1N1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets.

    abstract::A pandemic-capable influenza virus requires a hemagglutinin (HA) surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006276

    authors: Russier M,Yang G,Marinova-Petkova A,Vogel P,Kaplan BS,Webby RJ,Russell CJ

    更新日期:2017-03-10 00:00:00

  • Candida albicans white and opaque cells undergo distinct programs of filamentous growth.

    abstract::The ability to switch between yeast and filamentous forms is central to Candida albicans biology. The yeast-hyphal transition is implicated in adherence, tissue invasion, biofilm formation, phagocyte escape, and pathogenesis. A second form of morphological plasticity in C. albicans involves epigenetic switching betwee...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003210

    authors: Si H,Hernday AD,Hirakawa MP,Johnson AD,Bennett RJ

    更新日期:2013-03-01 00:00:00

  • Vibrio cholerae Response Regulator VxrB Controls Colonization and Regulates the Type VI Secretion System.

    abstract::Two-component signal transduction systems (TCS) are used by bacteria to sense and respond to their environment. TCS are typically composed of a sensor histidine kinase (HK) and a response regulator (RR). The Vibrio cholerae genome encodes 52 RR, but the role of these RRs in V. cholerae pathogenesis is largely unknown....

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004933

    authors: Cheng AT,Ottemann KM,Yildiz FH

    更新日期:2015-05-22 00:00:00

  • Acute Infectious Gastroenteritis Potentiates a Crohn's Disease Pathobiont to Fuel Ongoing Inflammation in the Post-Infectious Period.

    abstract::Crohn's disease (CD) is a chronic inflammatory condition of diverse etiology. Exposure to foodborne pathogens causing acute gastroenteritis produces a long-term risk of CD well into the post-infectious period but the mechanistic basis for this ongoing relationship to disease onset is unknown. We developed two novel mo...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005907

    authors: Small CL,Xing L,McPhee JB,Law HT,Coombes BK

    更新日期:2016-10-06 00:00:00

  • The pneumococcal serine-rich repeat protein is an intra-species bacterial adhesin that promotes bacterial aggregation in vivo and in biofilms.

    abstract::The Pneumococcal serine-rich repeat protein (PsrP) is a pathogenicity island encoded adhesin that has been positively correlated with the ability of Streptococcus pneumoniae to cause invasive disease. Previous studies have shown that PsrP mediates bacterial attachment to Keratin 10 (K10) on the surface of lung cells t...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001044

    authors: Sanchez CJ,Shivshankar P,Stol K,Trakhtenbroit S,Sullam PM,Sauer K,Hermans PW,Orihuela CJ

    更新日期:2010-08-12 00:00:00

  • A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody.

    abstract::Epitopes that are conserved among SARS-like coronaviruses are attractive targets for design of cross-reactive vaccines and therapeutics. CR3022 is a SARS-CoV neutralizing antibody to a highly conserved epitope on the receptor binding domain (RBD) on the spike protein that is able to cross-react with SARS-CoV-2, but wi...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1009089

    authors: Wu NC,Yuan M,Bangaru S,Huang D,Zhu X,Lee CD,Turner HL,Peng L,Yang L,Burton DR,Nemazee D,Ward AB,Wilson IA

    更新日期:2020-12-04 00:00:00

  • RNA interference analysis of Legionella in Drosophila cells: exploitation of early secretory apparatus dynamics.

    abstract::Legionella pneumophila translocates multiple bacterial effector proteins into host cells to direct formation of a replication vacuole for the bacterium. The emerging consensus is that formation of this compartment involves recruitment of membrane material that traffics between the endoplasmic reticulum (ER) and Golgi....

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0020034

    authors: Dorer MS,Kirton D,Bader JS,Isberg RR

    更新日期:2006-04-01 00:00:00

  • The EBNA3 family of Epstein-Barr virus nuclear proteins associates with the USP46/USP12 deubiquitination complexes to regulate lymphoblastoid cell line growth.

    abstract::The Epstein-Barr virus (EBV) nuclear proteins EBNA3A, EBNA3B, and EBNA3C interact with the cell DNA binding protein RBPJ and regulate cell and viral genes. Repression of the CDKN2A tumor suppressor gene products p16(INK4A) and p14(ARF) by EBNA3A and EBNA3C is critical for EBV mediated transformation of resting B lymph...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004822

    authors: Ohashi M,Holthaus AM,Calderwood MA,Lai CY,Krastins B,Sarracino D,Johannsen E

    更新日期:2015-04-09 00:00:00