Palmitoylation mediates membrane association of hepatitis E virus ORF3 protein and is required for infectious particle secretion.

Abstract:

:Hepatitis E virus (HEV) is a positive-strand RNA virus encoding 3 open reading frames (ORF). HEV ORF3 protein is a small, hitherto poorly characterized protein involved in viral particle secretion and possibly other functions. Here, we show that HEV ORF3 protein forms membrane-associated oligomers. Immunoblot analyses of ORF3 protein expressed in cell-free vs. cellular systems suggested a posttranslational modification. Further analyses revealed that HEV ORF3 protein is palmitoylated at cysteine residues in its N-terminal region, as corroborated by 3H-palmitate labeling, the investigation of cysteine-to-alanine substitution mutants and treatment with the palmitoylation inhibitor 2-bromopalmitate (2-BP). Abrogation of palmitoylation by site-directed mutagenesis or 2-BP treatment altered the subcellular localization of ORF3 protein, reduced the stability of the protein and strongly impaired the secretion of infectious particles. Moreover, selective membrane permeabilization coupled with immunofluorescence microscopy revealed that HEV ORF3 protein is entirely exposed to the cytosolic side of the membrane, allowing to propose a model for its membrane topology and interactions required in the viral life cycle. In conclusion, palmitoylation determines the subcellular localization, membrane topology and function of HEV ORF3 protein in the HEV life cycle.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Gouttenoire J,Pollán A,Abrami L,Oechslin N,Mauron J,Matter M,Oppliger J,Szkolnicka D,Dao Thi VL,van der Goot FG,Moradpour D

doi

10.1371/journal.ppat.1007471

subject

Has Abstract

pub_date

2018-12-10 00:00:00

pages

e1007471

issue

12

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-18-00685

journal_volume

14

pub_type

杂志文章
  • The Drosophila CD36 Homologue croquemort Is Required to Maintain Immune and Gut Homeostasis during Development and Aging.

    abstract::Phagocytosis is an ancient mechanism central to both tissue homeostasis and immune defense. Both the identity of the receptors that mediate bacterial phagocytosis and the nature of the interactions between phagocytosis and other defense mechanisms remain elusive. Here, we report that Croquemort (Crq), a Drosophila mem...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005961

    authors: Guillou A,Troha K,Wang H,Franc NC,Buchon N

    更新日期:2016-10-25 00:00:00

  • Structure Analysis Uncovers a Highly Diverse but Structurally Conserved Effector Family in Phytopathogenic Fungi.

    abstract::Phytopathogenic ascomycete fungi possess huge effector repertoires that are dominated by hundreds of sequence-unrelated small secreted proteins. The molecular function of these effectors and the evolutionary mechanisms that generate this tremendous number of singleton genes are largely unknown. To get a deeper underst...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005228

    authors: de Guillen K,Ortiz-Vallejo D,Gracy J,Fournier E,Kroj T,Padilla A

    更新日期:2015-10-27 00:00:00

  • Mycolactone-Dependent Depletion of Endothelial Cell Thrombomodulin Is Strongly Associated with Fibrin Deposition in Buruli Ulcer Lesions.

    abstract::A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surf...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005011

    authors: Ogbechi J,Ruf MT,Hall BS,Bodman-Smith K,Vogel M,Wu HL,Stainer A,Esmon CT,Ahnström J,Pluschke G,Simmonds RE

    更新日期:2015-07-16 00:00:00

  • Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure.

    abstract::Ebolavirus (EBOV), the causative agent of a severe hemorrhagic fever and a biosafety level 4 pathogen, increases its genome coding capacity by producing multiple transcripts encoding for structural and nonstructural glycoproteins from a single gene. This is achieved through RNA editing, during which non-template adeno...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003677

    authors: Mehedi M,Hoenen T,Robertson S,Ricklefs S,Dolan MA,Taylor T,Falzarano D,Ebihara H,Porcella SF,Feldmann H

    更新日期:2013-01-01 00:00:00

  • Characterization of reemerging chikungunya virus.

    abstract::An unprecedented epidemic of chikungunya virus (CHIKV) infection recently started in countries of the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The basis for chikungunya disease and the tropism of CHIKV remain unkno...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0030089

    authors: Sourisseau M,Schilte C,Casartelli N,Trouillet C,Guivel-Benhassine F,Rudnicka D,Sol-Foulon N,Le Roux K,Prevost MC,Fsihi H,Frenkiel MP,Blanchet F,Afonso PV,Ceccaldi PE,Ozden S,Gessain A,Schuffenecker I,Verhasselt B,Zamb

    更新日期:2007-06-01 00:00:00

  • Titan cells formation in Cryptococcus neoformans is finely tuned by environmental conditions and modulated by positive and negative genetic regulators.

    abstract::The pathogenic fungus Cryptococcus neoformans exhibits morphological changes in cell size during lung infection, producing both typical size 5 to 7 μm cells and large titan cells (> 10 μm and up to 100 μm). We found and optimized in vitro conditions that produce titan cells in order to identify the ancestry of titan c...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006982

    authors: Hommel B,Mukaremera L,Cordero RJB,Coelho C,Desjardins CA,Sturny-Leclère A,Janbon G,Perfect JR,Fraser JA,Casadevall A,Cuomo CA,Dromer F,Nielsen K,Alanio A

    更新日期:2018-05-18 00:00:00

  • DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target.

    abstract::Dengue is the most common mosquito-borne viral disease in humans. Changes of lipid-related metabolites in endoplasmic reticulum of dengue virus (DENV) infected cells have been associated with replicative complexes formation. Previously, we reported that DENV infection inhibits HMGCR phosphorylation generating a choles...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006257

    authors: Soto-Acosta R,Bautista-Carbajal P,Cervantes-Salazar M,Angel-Ambrocio AH,Del Angel RM

    更新日期:2017-04-06 00:00:00

  • Critical role of Bcr1-dependent adhesins in C. albicans biofilm formation in vitro and in vivo.

    abstract::The fungal pathogen Candida albicans is frequently associated with catheter-based infections because of its ability to form resilient biofilms. Prior studies have shown that the transcription factor Bcr1 governs biofilm formation in an in vitro catheter model. However, the mechanistic role of the Bcr1 pathway and its ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0020063

    authors: Nobile CJ,Andes DR,Nett JE,Smith FJ,Yue F,Phan QT,Edwards JE,Filler SG,Mitchell AP

    更新日期:2006-07-01 00:00:00

  • Dependence of intracellular and exosomal microRNAs on viral E6/E7 oncogene expression in HPV-positive tumor cells.

    abstract::Specific types of human papillomaviruses (HPVs) cause cervical cancer. Cervical cancers exhibit aberrant cellular microRNA (miRNA) expression patterns. By genome-wide analyses, we investigate whether the intracellular and exosomal miRNA compositions of HPV-positive cancer cells are dependent on endogenous E6/E7 oncoge...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004712

    authors: Honegger A,Schilling D,Bastian S,Sponagel J,Kuryshev V,Sültmann H,Scheffner M,Hoppe-Seyler K,Hoppe-Seyler F

    更新日期:2015-03-11 00:00:00

  • Assessing predicted HIV-1 replicative capacity in a clinical setting.

    abstract::HIV-1 replicative capacity (RC) provides a measure of within-host fitness and is determined in the context of phenotypic drug resistance testing. However it is unclear how these in-vitro measurements relate to in-vivo processes. Here we assess RCs in a clinical setting by combining a previously published machine-learn...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002321

    authors: Kouyos RD,von Wyl V,Hinkley T,Petropoulos CJ,Haddad M,Whitcomb JM,Böni J,Yerly S,Cellerai C,Klimkait T,Günthard HF,Bonhoeffer S,Swiss HIV Cohort Study.

    更新日期:2011-11-01 00:00:00

  • Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger.

    abstract::Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Currently, how EBOV fuses its envelope membrane within an endosomal membrane to cause infection is poorly understood. We successfully measure cell-cell fusion mediated by the EBOV fusion protein, GP, assayed by the...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005373

    authors: Markosyan RM,Miao C,Zheng YM,Melikyan GB,Liu SL,Cohen FS

    更新日期:2016-01-05 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

  • Crystal structure of Mokola virus glycoprotein in its post-fusion conformation.

    abstract::Mokola virus (MOKV) belongs to the lyssavirus genus. As other genus members-including rabies virus (RABV)-it causes deadly encephalitis in mammals. MOKV entry into host cells is mediated by its transmembrane glycoprotein G. First, G binds cellular receptors, triggering virion endocytosis. Then, in the acidic endosomal...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008383

    authors: Belot L,Ouldali M,Roche S,Legrand P,Gaudin Y,Albertini AA

    更新日期:2020-03-09 00:00:00

  • A Role for the SmpB-SsrA system in Yersinia pseudotuberculosis pathogenesis.

    abstract::Yersinia utilizes a sophisticated type III secretion system to enhance its chances of survival and to overcome the host immune system. SmpB (small protein B) and SsrA (small stable RNA A) are components of a unique bacterial translational control system that help maintain the bacterial translational machinery in a ful...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0020006

    authors: Okan NA,Bliska JB,Karzai AW

    更新日期:2006-01-01 00:00:00

  • Trypanin, a component of the flagellar Dynein regulatory complex, is essential in bloodstream form African trypanosomes.

    abstract::The Trypanosoma brucei flagellum is a multifunctional organelle with critical roles in motility, cellular morphogenesis, and cell division. Although motility is thought to be important throughout the trypanosome lifecycle, most studies of flagellum structure and function have been restricted to the procyclic lifecycle...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0020101

    authors: Ralston KS,Hill KL

    更新日期:2006-09-01 00:00:00

  • CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus.

    abstract::Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. The bona fide receptor for HNoV is unknown. Recently, we identified CD300lf as a proteinaceous receptor for ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008242

    authors: Graziano VR,Walker FC,Kennedy EA,Wei J,Ettayebi K,Strine MS,Filler RB,Hassan E,Hsieh LL,Kim AS,Kolawole AO,Wobus CE,Lindesmith LC,Baric RS,Estes MK,Orchard RC,Baldridge MT,Wilen CB

    更新日期:2020-04-06 00:00:00

  • Tbet Deficiency Causes T Helper Cell Dependent Airways Eosinophilia and Mucus Hypersecretion in Response to Rhinovirus Infection.

    abstract::Current understanding of adaptive immune, particularly T cell, responses to human rhinoviruses (RV) is limited. Memory T cells are thought to be of a primarily T helper 1 type, but both T helper 1 and T helper 2 memory cells have been described, and heightened T helper 2/ lessened T helper 1 responses have been associ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005913

    authors: Glanville N,Peel TJ,Schröder A,Aniscenko J,Walton RP,Finotto S,Johnston SL

    更新日期:2016-09-28 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

  • SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products.

    abstract::Simian virus 40 (SV40) and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulatio...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004536

    authors: Sowd GA,Mody D,Eggold J,Cortez D,Friedman KL,Fanning E

    更新日期:2014-12-04 00:00:00

  • Histone H2B-IFI16 Recognition of Nuclear Herpesviral Genome Induces Cytoplasmic Interferon-β Responses.

    abstract::IFI16 (gamma-interferon-inducible protein 16), a predominantly nuclear protein involved in transcriptional regulation, also functions as an innate immune response DNA sensor and induces the IL-1β and antiviral type-1 interferon-β (IFN-β) cytokines. We have shown that IFI16, in association with BRCA1, functions as a se...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005967

    authors: Iqbal J,Ansari MA,Kumar B,Dutta D,Roy A,Chikoti L,Pisano G,Dutta S,Vahedi S,Veettil MV,Chandran B

    更新日期:2016-10-20 00:00:00

  • Crystal Structure of the Human Cytomegalovirus Glycoprotein B.

    abstract::Human cytomegalovirus (HCMV), a dsDNA, enveloped virus, is a ubiquitous pathogen that establishes lifelong latent infections and caused disease in persons with compromised immune systems, e.g., organ transplant recipients or AIDS patients. HCMV is also a leading cause of congenital viral infections in newborns. Entry ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005227

    authors: Burke HG,Heldwein EE

    更新日期:2015-10-20 00:00:00

  • COP1, a negative regulator of photomorphogenesis, positively regulates plant disease resistance via double-stranded RNA binding proteins.

    abstract::The E3 ubiquitin ligase COP1 (Constitutive Photomorphogenesis 1) is a well known component of the light-mediated plant development that acts as a repressor of photomorphogenesis. Here we show that COP1 positively regulates defense against turnip crinkle virus (TCV) and avrRPM1 bacteria by contributing to stability of ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006894

    authors: Lim GH,Hoey T,Zhu S,Clavel M,Yu K,Navarre D,Kachroo A,Deragon JM,Kachroo P

    更新日期:2018-03-07 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

  • Identification of site-specific adaptations conferring increased neural cell tropism during human enterovirus 71 infection.

    abstract::Enterovirus 71 (EV71) is one of the most virulent enteroviruses, but the specific molecular features that enhance its ability to disseminate in humans remain unknown. We analyzed the genomic features of EV71 in an immunocompromised host with disseminated disease according to the different sites of infection. Compariso...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002826

    authors: Cordey S,Petty TJ,Schibler M,Martinez Y,Gerlach D,van Belle S,Turin L,Zdobnov E,Kaiser L,Tapparel C

    更新日期:2012-01-01 00:00:00

  • Key interplay between the co-opted sorting nexin-BAR proteins and PI3P phosphoinositide in the formation of the tombusvirus replicase.

    abstract::Positive-strand RNA viruses replicate in host cells by forming large viral replication organelles, which harbor numerous membrane-bound viral replicase complexes (VRCs). In spite of its essential role in viral replication, the biogenesis of the VRCs is not fully understood. The authors identified critical roles of cel...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1009120

    authors: Feng Z,Kovalev N,Nagy PD

    更新日期:2020-12-28 00:00:00

  • Cell-length heterogeneity: a population-level solution to growth/virulence trade-offs in the plant pathogen Dickeya dadantii.

    abstract::Necrotrophic plant pathogens acquire nutrients from dead plant cells, which requires the disintegration of the plant cell wall and tissue structures by the pathogen. Infected plants lose tissue integrity and functional immunity as a result, exposing the nutrient rich, decayed tissues to the environment. One challenge ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007703

    authors: Cui Z,Yang CH,Kharadi RR,Yuan X,Sundin GW,Triplett LR,Wang J,Zeng Q

    更新日期:2019-08-05 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

  • Induction of type I interferon signaling determines the relative pathogenicity of Staphylococcus aureus strains.

    abstract::The tremendous success of S. aureus as a human pathogen has been explained primarily by its array of virulence factors that enable the organism to evade host immunity. Perhaps equally important, but less well understood, is the importance of the intensity of the host response in determining the extent of pathology ind...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003951

    authors: Parker D,Planet PJ,Soong G,Narechania A,Prince A

    更新日期:2014-02-20 00:00:00

  • Prolonged influenza virus shedding and emergence of antiviral resistance in immunocompromised patients and ferrets.

    abstract::Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitt...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003343

    authors: van der Vries E,Stittelaar KJ,van Amerongen G,Veldhuis Kroeze EJ,de Waal L,Fraaij PL,Meesters RJ,Luider TM,van der Nagel B,Koch B,Vulto AG,Schutten M,Osterhaus AD

    更新日期:2013-01-01 00:00:00

  • Phage resistance at the cost of virulence: Listeria monocytogenes serovar 4b requires galactosylated teichoic acids for InlB-mediated invasion.

    abstract::The intracellular pathogen Listeria monocytogenes is distinguished by its ability to invade and replicate within mammalian cells. Remarkably, of the 15 serovars within the genus, strains belonging to serovar 4b cause the majority of listeriosis clinical cases and outbreaks. The Listeria O-antigens are defined by subtl...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008032

    authors: Sumrall ET,Shen Y,Keller AP,Rismondo J,Pavlou M,Eugster MR,Boulos S,Disson O,Thouvenot P,Kilcher S,Wollscheid B,Cabanes D,Lecuit M,Gründling A,Loessner MJ

    更新日期:2019-10-07 00:00:00