EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis.

Abstract:

:Epstein-Barr virus (EBV) is a ubiquitous oncogenic virus that induces many cancers. N6-Methyladenosine (m6A) modification regulates many cellular processes. We explored the role of m6A in EBV gene regulation and associated cancers. We have comprehensively defined m6A modification of EBV latent and lytic transcripts. Furthermore, m6A modification demonstrated a functional role in regulation of the stability of viral transcripts. The methyltransferase METTL14 was induced at the transcript and protein levels, and knock-down of METTL14 led to decreased expression of latent EBV transcripts. METTL14 was also significantly induced in EBV-positive tumors, promoted growth of EBV-transformed cells and tumors in Xenograft animal models. Mechanistically, the viral-encoded latent oncoprotein EBNA3C activated transcription of METTL14, and directly interacted with METTL14 to promote its stability. This demonstrated that EBV hijacks METTL14 to drive EBV-mediated tumorigenesis. METTL14 is now a new target for development of therapeutics for treatment of EBV-associated cancers.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Lang F,Singh RK,Pei Y,Zhang S,Sun K,Robertson ES

doi

10.1371/journal.ppat.1007796

subject

Has Abstract

pub_date

2019-06-21 00:00:00

pages

e1007796

issue

6

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-19-00015

journal_volume

15

pub_type

杂志文章
  • Structural and immunologic correlates of chemically stabilized HIV-1 envelope glycoproteins.

    abstract::Inducing broad spectrum neutralizing antibodies against challenging pathogens such as HIV-1 is a major vaccine design goal, but may be hindered by conformational instability within viral envelope glycoproteins (Env). Chemical cross-linking is widely used for vaccine antigen stabilization, but how this process affects ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006986

    authors: Schiffner T,Pallesen J,Russell RA,Dodd J,de Val N,LaBranche CC,Montefiori D,Tomaras GD,Shen X,Harris SL,Moghaddam AE,Kalyuzhniy O,Sanders RW,McCoy LE,Moore JP,Ward AB,Sattentau QJ

    更新日期:2018-05-10 00:00:00

  • Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza.

    abstract::Pandemic influenza A virus (IAV) remains a significant threat to global health. Preparedness relies primarily upon a single class of neuraminidase (NA) targeted antivirals, against which resistance is steadily growing. The M2 proton channel is an alternative clinically proven antiviral target, yet a near-ubiquitous S3...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008716

    authors: Scott C,Kankanala J,Foster TL,Goldhill DH,Bao P,Simmons K,Pingen M,Bentham M,Atkins E,Loundras E,Elderfield R,Claridge JK,Thompson J,Stilwell PR,Tathineni R,McKimmie CS,Targett-Adams P,Schnell JR,Cook GP,Evans S,B

    更新日期:2020-08-11 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

  • Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines.

    abstract::CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of ge...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006064

    authors: Gasper DJ,Neldner B,Plisch EH,Rustom H,Carrow E,Imai H,Kawaoka Y,Suresh M

    更新日期:2016-12-20 00:00:00

  • The Prolyl Isomerase Pin1 Promotes the Herpesvirus-Induced Phosphorylation-Dependent Disassembly of the Nuclear Lamina Required for Nucleocytoplasmic Egress.

    abstract::The nuclear lamina lines the inner nuclear membrane providing a structural framework for the nucleus. Cellular processes, such as nuclear envelope breakdown during mitosis or nuclear export of large ribonucleoprotein complexes, are functionally linked to the disassembly of the nuclear lamina. In general, lamina disass...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005825

    authors: Milbradt J,Hutterer C,Bahsi H,Wagner S,Sonntag E,Horn AH,Kaufer BB,Mori Y,Sticht H,Fossen T,Marschall M

    更新日期:2016-08-24 00:00:00

  • Ex vivo activation of CD4+ T-cells from donors on suppressive ART can lead to sustained production of infectious HIV-1 from a subset of infected cells.

    abstract::The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006230

    authors: Bui JK,Halvas EK,Fyne E,Sobolewski MD,Koontz D,Shao W,Luke B,Hong FF,Kearney MF,Mellors JW

    更新日期:2017-02-22 00:00:00

  • Helicobacter pylori perturbs iron trafficking in the epithelium to grow on the cell surface.

    abstract::Helicobacter pylori (Hp) injects the CagA effector protein into host epithelial cells and induces growth factor-like signaling, perturbs cell-cell junctions, and alters host cell polarity. This enables Hp to grow as microcolonies adhered to the host cell surface even in conditions that do not support growth of free-sw...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002050

    authors: Tan S,Noto JM,Romero-Gallo J,Peek RM Jr,Amieva MR

    更新日期:2011-05-01 00:00:00

  • Histone H1 plays a role in heterochromatin formation and VSG expression site silencing in Trypanosoma brucei.

    abstract::The African sleeping sickness parasite Trypanosoma brucei evades the host immune system through antigenic variation of its variant surface glycoprotein (VSG) coat. Although the T. brucei genome contains ∼1500 VSGs, only one VSG is expressed at a time from one of about 15 subtelomeric VSG expression sites (ESs). For an...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003010

    authors: Povelones ML,Gluenz E,Dembek M,Gull K,Rudenko G

    更新日期:2012-01-01 00:00:00

  • Loss of CNFY toxin-induced inflammation drives Yersinia pseudotuberculosis into persistency.

    abstract::Gastrointestinal infections caused by enteric yersiniae can become persistent and complicated by relapsing enteritis and severe autoimmune disorders. To establish a persistent infection, the bacteria have to cope with hostile surroundings when they transmigrate through the intestinal epithelium and colonize underlying...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006858

    authors: Heine W,Beckstette M,Heroven AK,Thiemann S,Heise U,Nuss AM,Pisano F,Strowig T,Dersch P

    更新日期:2018-02-01 00:00:00

  • Fatty acid DSF binds and allosterically activates histidine kinase RpfC of phytopathogenic bacterium Xanthomonas campestris pv. campestris to regulate quorum-sensing and virulence.

    abstract::As well as their importance to nutrition, fatty acids (FA) represent a unique group of quorum sensing chemicals that modulate the behavior of bacterial population in virulence. However, the way in which full-length, membrane-bound receptors biochemically detect FA remains unclear. Here, we provide genetic, enzymologic...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006304

    authors: Cai Z,Yuan ZH,Zhang H,Pan Y,Wu Y,Tian XQ,Wang FF,Wang L,Qian W

    更新日期:2017-04-03 00:00:00

  • Importin β Can Bind Hepatitis B Virus Core Protein and Empty Core-Like Particles and Induce Structural Changes.

    abstract::Hepatitis B virus (HBV) capsids are found in many forms: immature single-stranded RNA-filled cores, single-stranded DNA-filled replication intermediates, mature cores with relaxed circular double-stranded DNA, and empty capsids. A capsid, the protein shell of the core, is a complex of 240 copies of core protein. Matur...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005802

    authors: Chen C,Wang JC,Pierson EE,Keifer DZ,Delaleau M,Gallucci L,Cazenave C,Kann M,Jarrold MF,Zlotnick A

    更新日期:2016-08-12 00:00:00

  • Double-Edge Sword of Sustained ROCK Activation in Prion Diseases through Neuritogenesis Defects and Prion Accumulation.

    abstract::In prion diseases, synapse dysfunction, axon retraction and loss of neuronal polarity precede neuronal death. The mechanisms driving such polarization defects, however, remain unclear. Here, we examined the contribution of RhoA-associated coiled-coil containing kinases (ROCK), key players in neuritogenesis, to prion d...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005073

    authors: Alleaume-Butaux A,Nicot S,Pietri M,Baudry A,Dakowski C,Tixador P,Ardila-Osorio H,Haeberlé AM,Bailly Y,Peyrin JM,Launay JM,Kellermann O,Schneider B

    更新日期:2015-08-04 00:00:00

  • Mycobacterium tuberculosis uses host triacylglycerol to accumulate lipid droplets and acquires a dormancy-like phenotype in lipid-loaded macrophages.

    abstract::Two billion people are latently infected with Mycobacterium tuberculosis (Mtb). Mtb-infected macrophages are likely to be sequestered inside the hypoxic environments of the granuloma and differentiate into lipid-loaded macrophages that contain triacylglycerol (TAG)-filled lipid droplets which may provide a fatty acid-...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002093

    authors: Daniel J,Maamar H,Deb C,Sirakova TD,Kolattukudy PE

    更新日期:2011-06-01 00:00:00

  • Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site.

    abstract::Eliciting broad tier 2 neutralizing antibodies (nAbs) is a major goal of HIV-1 vaccine research. Here we investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit nAbs. Unusually potent nAb titers developed in 2 of 8 rabbits immunized with virus-like particles (VLPs) expressing trimers (trimer...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004932

    authors: Crooks ET,Tong T,Chakrabarti B,Narayan K,Georgiev IS,Menis S,Huang X,Kulp D,Osawa K,Muranaka J,Stewart-Jones G,Destefano J,O'Dell S,LaBranche C,Robinson JE,Montefiori DC,McKee K,Du SX,Doria-Rose N,Kwong PD,Mascola

    更新日期:2015-05-29 00:00:00

  • Differences in APOBEC3G expression in CD4+ T helper lymphocyte subtypes modulate HIV-1 infectivity.

    abstract::The cytidine deaminases APOBEC3G and APOBEC3F exert anti-HIV-1 activity that is countered by the HIV-1 vif protein. Based on potential transcription factor binding sites in their putative promoters, we hypothesized that expression of APOBEC3G and APOBEC3F would vary with T helper lymphocyte differentiation. Naive CD4+...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000292

    authors: Vetter ML,Johnson ME,Antons AK,Unutmaz D,D'Aquila RT

    更新日期:2009-02-01 00:00:00

  • Prion shedding from olfactory neurons into nasal secretions.

    abstract::This study investigated the role of prion infection of the olfactory mucosa in the shedding of prion infectivity into nasal secretions. Prion infection with the HY strain of the transmissible mink encephalopathy (TME) agent resulted in a prominent infection of the olfactory bulb and the olfactory sensory epithelium in...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000837

    authors: Bessen RA,Shearin H,Martinka S,Boharski R,Lowe D,Wilham JM,Caughey B,Wiley JA

    更新日期:2010-04-15 00:00:00

  • The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells.

    abstract::Coronavirus replication takes place in the host cell cytoplasm and triggers inflammatory gene expression by poorly characterized mechanisms. To obtain more insight into the signals and molecular events that coordinate global host responses in the nucleus of coronavirus-infected cells, first, transcriptome dynamics was...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006286

    authors: Poppe M,Wittig S,Jurida L,Bartkuhn M,Wilhelm J,Müller H,Beuerlein K,Karl N,Bhuju S,Ziebuhr J,Schmitz ML,Kracht M

    更新日期:2017-03-29 00:00:00

  • Identification of an Acinetobacter baumannii zinc acquisition system that facilitates resistance to calprotectin-mediated zinc sequestration.

    abstract::Acinetobacter baumannii is an important nosocomial pathogen that accounts for up to 20 percent of infections in intensive care units worldwide. Furthermore, A. baumannii strains have emerged that are resistant to all available antimicrobials. These facts highlight the dire need for new therapeutic strategies to combat...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003068

    authors: Hood MI,Mortensen BL,Moore JL,Zhang Y,Kehl-Fie TE,Sugitani N,Chazin WJ,Caprioli RM,Skaar EP

    更新日期:2012-01-01 00:00:00

  • NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus.

    abstract::A global increase in invasive infections due to group A Streptococcus (S. pyogenes or GAS) has been observed since the 1980s, associated with emergence of a clonal group of strains of the M1T1 serotype. Among other virulence attributes, the M1T1 clone secretes NAD+-glycohydrolase (NADase). When GAS binds to epithelial...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005468

    authors: Sharma O,O'Seaghdha M,Velarde JJ,Wessels MR

    更新日期:2016-03-03 00:00:00

  • Preservation of tetherin and CD4 counter-activities in circulating Vpu alleles despite extensive sequence variation within HIV-1 infected individuals.

    abstract::The HIV-1 Vpu protein is expressed from a bi-cistronic message late in the viral life cycle. It functions during viral assembly to maximise infectious virus release by targeting CD4 for proteosomal degradation and counteracting the antiviral protein tetherin (BST2/CD317). Single genome analysis of vpu repertoires thro...

    journal_title:PLoS pathogens

    pub_type: 临床试验,杂志文章

    doi:10.1371/journal.ppat.1003895

    authors: Pickering S,Hué S,Kim EY,Reddy S,Wolinsky SM,Neil SJ

    更新日期:2014-01-01 00:00:00

  • Yersinia pseudotuberculosis YopH targets SKAP2-dependent and independent signaling pathways to block neutrophil antimicrobial mechanisms during infection.

    abstract::Yersinia suppress neutrophil responses by using a type 3 secretion system (T3SS) to inject 6-7 Yersinia effector proteins (Yops) effectors into their cytoplasm. YopH is a tyrosine phosphatase that causes dephosphorylation of the adaptor protein SKAP2, among other targets in neutrophils. SKAP2 functions in reactive oxy...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008576

    authors: Shaban L,Nguyen GT,Mecsas-Faxon BD,Swanson KD,Tan S,Mecsas J

    更新日期:2020-05-11 00:00:00

  • De novo synthesis of VP16 coordinates the exit from HSV latency in vivo.

    abstract::The mechanism controlling the exit from herpes simplex virus latency (HSV) is of central importance to recurrent disease and transmission of infection, yet interactions between host and viral functions that govern this process remain unclear. The cascade of HSV gene transcription is initiated by the multifunctional vi...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000352

    authors: Thompson RL,Preston CM,Sawtell NM

    更新日期:2009-03-01 00:00:00

  • Plant NLR immune receptor Tm-22 activation requires NB-ARC domain-mediated self-association of CC domain.

    abstract::The nucleotide-binding, leucine-rich repeat-containing (NLR) class of immune receptors of plants and animals recognize pathogen-encoded proteins and trigger host defenses. Although animal NLRs form oligomers upon pathogen recognition to activate downstream signaling, the mechanisms of plant NLR activation remain large...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008475

    authors: Wang J,Chen T,Han M,Qian L,Li J,Wu M,Han T,Cao J,Nagalakshmi U,Rathjen JP,Hong Y,Liu Y

    更新日期:2020-04-27 00:00:00

  • IFNγ signaling endows DCs with the capacity to control type I inflammation during parasitic infection through promoting T-bet+ regulatory T cells.

    abstract::IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004635

    authors: Lee HM,Fleige A,Forman R,Cho S,Khan AA,Lin LL,Nguyen DT,O'Hara-Hall A,Yin Z,Hunter CA,Muller W,Lu LF

    更新日期:2015-02-06 00:00:00

  • Polarized Cell Division of Chlamydia trachomatis.

    abstract::Bacterial cell division predominantly occurs by a highly conserved process, termed binary fission, that requires the bacterial homologue of tubulin, FtsZ. Other mechanisms of bacterial cell division that are independent of FtsZ are rare. Although the obligate intracellular human pathogen Chlamydia trachomatis, the lea...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005822

    authors: Abdelrahman Y,Ouellette SP,Belland RJ,Cox JV

    更新日期:2016-08-09 00:00:00

  • The Replicative Consequences of Papillomavirus E2 Protein Binding to the Origin Replication Factor ORC2.

    abstract::The origin recognition complex (ORC) coordinates a series of events that lead to initiation of DNA strand duplication. As a nuclear double stranded DNA plasmid, the papillomavirus (PV) genome resembles a mini-chromosome in infected cells. To initiate its replication, the viral E2 protein binds to and recruits the E1 D...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005934

    authors: DeSmet M,Kanginakudru S,Rietz A,Wu WH,Roden R,Androphy EJ

    更新日期:2016-10-04 00:00:00

  • Processing of nuclear viroids in vivo: an interplay between RNA conformations.

    abstract::Replication of viroids, small non-protein-coding plant pathogenic RNAs, entails reiterative transcription of their incoming single-stranded circular genomes, to which the (+) polarity is arbitrarily assigned, cleavage of the oligomeric strands of one or both polarities to unit-length, and ligation to circular RNAs. Wh...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0030182

    authors: Gas ME,Hernández C,Flores R,Daròs JA

    更新日期:2007-11-01 00:00:00

  • Limited HIV-2 reservoirs in central-memory CD4 T-cells associated to CXCR6 co-receptor expression in attenuated HIV-2 infection.

    abstract::The low pathogenicity and replicative potential of HIV-2 are still poorly understood. We investigated whether HIV-2 reservoirs might follow the peculiar distribution reported in models of attenuated HIV-1/SIV infections, i.e. limited infection of central-memory CD4 T lymphocytes (TCM). Antiretroviral-naive HIV-2 infec...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007758

    authors: Samri A,Charpentier C,Diallo MS,Bertine M,Even S,Morin V,Oudin A,Parizot C,Collin G,Hosmalin A,Cheynier R,Thiébaut R,Matheron S,Collin F,Zoorob R,Brun-Vézinet F,Autran B,ANRS CO5 IMMUNOVIR-2 Study Group.

    更新日期:2019-05-16 00:00:00

  • Newly discovered ebola virus associated with hemorrhagic fever outbreak in Uganda.

    abstract::Over the past 30 years, Zaire and Sudan ebolaviruses have been responsible for large hemorrhagic fever (HF) outbreaks with case fatalities ranging from 53% to 90%, while a third species, Côte d'Ivoire ebolavirus, caused a single non-fatal HF case. In November 2007, HF cases were reported in Bundibugyo District, Wester...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000212

    authors: Towner JS,Sealy TK,Khristova ML,Albariño CG,Conlan S,Reeder SA,Quan PL,Lipkin WI,Downing R,Tappero JW,Okware S,Lutwama J,Bakamutumaho B,Kayiwa J,Comer JA,Rollin PE,Ksiazek TG,Nichol ST

    更新日期:2008-11-01 00:00:00

  • Type I J-domain NbMIP1 proteins are required for both Tobacco mosaic virus infection and plant innate immunity.

    abstract::Tm-2² is a coiled coil-nucleotide binding-leucine rich repeat resistance protein that confers durable extreme resistance against Tomato mosaic virus (ToMV) and Tobacco mosaic virus (TMV) by recognizing the viral movement protein (MP). Here we report that the Nicotiana benthamiana J-domain MIP1 proteins (NbMIP1s) assoc...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003659

    authors: Du Y,Zhao J,Chen T,Liu Q,Zhang H,Wang Y,Hong Y,Xiao F,Zhang L,Shen Q,Liu Y

    更新日期:2013-01-01 00:00:00