Dengue virus reduces AGPAT1 expression to alter phospholipids and enhance infection in Aedes aegypti.

Abstract:

:More than half of the world population is at risk of dengue virus (DENV) infection because of the global distribution of its mosquito vectors. DENV is an envelope virus that relies on host lipid membranes for its life-cycle. Here, we characterized how DENV hijacks the mosquito lipidome to identify targets for novel transmission-blocking interventions. To describe metabolic changes throughout the mosquito DENV cycle, we deployed a Liquid chromatography-high resolution mass spectrometry (LC-HRMS) workflow including spectral similarity annotation in cells, midguts and whole mosquitoes at different times post infection. We revealed a major aminophospholipid reconfiguration with an overall early increase, followed by a reduction later in the cycle. We phylogenetically characterized acylglycerolphosphate acyltransferase (AGPAT) enzyme isoforms to identify those that catalyze a rate-limiting step in phospholipid biogenesis, the acylation of lysophosphatidate to phosphatidate. We showed that DENV infection decreased AGPAT1, but did not alter AGPAT2 expression in cells, midguts and mosquitoes. Depletion of either AGPAT1 or AGPAT2 increased aminophospholipids and partially recapitulated DENV-induced reconfiguration before infection in vitro. However, only AGPAT1 depletion promoted infection by maintaining high aminophospholipid concentrations. In mosquitoes, AGPAT1 depletion also partially recapitulated DENV-induced aminophospholipid increase before infection and enhanced infection by maintaining high aminophospholipid concentrations. These results indicate that DENV inhibition of AGPAT1 expression promotes infection by increasing aminophospholipids, as observed in the mosquito's early DENV cycle. Furthermore, in AGPAT1-depleted mosquitoes, we showed that enhanced infection was associated with increased consumption/redirection of aminophospholipids. Our study suggests that DENV regulates aminophospholipids, especially phosphatidylcholine and phosphatidylethanolamine, by inhibiting AGPAT1 expression to increase aminophospholipid availability for virus multiplication.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Vial T,Tan WL,Wong Wei Xiang B,Missé D,Deharo E,Marti G,Pompon J

doi

10.1371/journal.ppat.1008199

subject

Has Abstract

pub_date

2019-12-09 00:00:00

pages

e1008199

issue

12

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-19-00992

journal_volume

15

pub_type

杂志文章
  • Disruption of PML nuclear bodies is mediated by ORF61 SUMO-interacting motifs and required for varicella-zoster virus pathogenesis in skin.

    abstract::Promyelocytic leukemia protein (PML) has antiviral functions and many viruses encode gene products that disrupt PML nuclear bodies (PML NBs). However, evidence of the relevance of PML NB modification for viral pathogenesis is limited and little is known about viral gene functions required for PML NB disruption in infe...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002157

    authors: Wang L,Oliver SL,Sommer M,Rajamani J,Reichelt M,Arvin AM

    更新日期:2011-08-01 00:00:00

  • Signal peptidase complex subunit 1 participates in the assembly of hepatitis C virus through an interaction with E2 and NS2.

    abstract::Hepatitis C virus (HCV) nonstructural protein 2 (NS2) is a hydrophobic, transmembrane protein that is required not only for NS2-NS3 cleavage, but also for infectious virus production. To identify cellular factors that interact with NS2 and are important for HCV propagation, we screened a human liver cDNA library by sp...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003589

    authors: Suzuki R,Matsuda M,Watashi K,Aizaki H,Matsuura Y,Wakita T,Suzuki T

    更新日期:2013-01-01 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

  • HPV16-E7 expression in squamous epithelium creates a local immune suppressive environment via CCL2- and CCL5- mediated recruitment of mast cells.

    abstract::Human Papillomavirus (HPV) 16 E7 protein promotes the transformation of HPV infected epithelium to malignancy. Here, we use a murine model in which the E7 protein of HPV16 is expressed as a transgene in epithelium to show that mast cells are recruited to the basal layer of E7-expressing epithelium, and that this recru...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004466

    authors: Bergot AS,Ford N,Leggatt GR,Wells JW,Frazer IH,Grimbaldeston MA

    更新日期:2014-10-23 00:00:00

  • Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.

    abstract::Interferons (IFNs) are a group of cytokines with a well-established antiviral function. They can be induced by viral infection, are secreted and bind to specific receptors on the same or neighbouring cells to activate the expression of hundreds of IFN stimulated genes (ISGs) with antiviral function. Type I IFN has bee...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003773

    authors: Crotta S,Davidson S,Mahlakoiv T,Desmet CJ,Buckwalter MR,Albert ML,Staeheli P,Wack A

    更新日期:2013-01-01 00:00:00

  • Programmed protection of foreign DNA from restriction allows pathogenicity island exchange during pneumococcal transformation.

    abstract::In bacteria, transformation and restriction-modification (R-M) systems play potentially antagonistic roles. While the former, proposed as a form of sexuality, relies on internalized foreign DNA to create genetic diversity, the latter degrade foreign DNA to protect from bacteriophage attack. The human pathogen Streptoc...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003178

    authors: Johnston C,Martin B,Granadel C,Polard P,Claverys JP

    更新日期:2013-02-01 00:00:00

  • Phage-mediated dispersal of biofilm and distribution of bacterial virulence genes is induced by quorum sensing.

    abstract::The microbiome and the phage meta-genome within the human gut are influenced by antibiotic treatments. Identifying a novel mechanism, here we demonstrate that bacteria use the universal communication molecule AI-2 to induce virulence genes and transfer them via phage release. High concentrations (i.e. 100 μM) of AI-2 ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004653

    authors: Rossmann FS,Racek T,Wobser D,Puchalka J,Rabener EM,Reiger M,Hendrickx AP,Diederich AK,Jung K,Klein C,Huebner J

    更新日期:2015-02-23 00:00:00

  • Definition of herpes simplex virus type 1 helper activities for adeno-associated virus early replication events.

    abstract::The human parvovirus Adeno-Associated Virus (AAV) type 2 can only replicate in cells co-infected with a helper virus, such as Adenovirus or Herpes Simplex Virus type 1 (HSV-1); whereas, in the absence of a helper virus, it establishes a latent infection. Previous studies demonstrated that the ternary HSV-1 helicase/pr...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000340

    authors: Alazard-Dany N,Nicolas A,Ploquin A,Strasser R,Greco A,Epstein AL,Fraefel C,Salvetti A

    更新日期:2009-03-01 00:00:00

  • Innate killing of Leishmania donovani by macrophages of the splenic marginal zone requires IRF-7.

    abstract::Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ aft...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000813

    authors: Phillips R,Svensson M,Aziz N,Maroof A,Brown N,Beattie L,Signoret N,Kaye PM

    更新日期:2010-03-12 00:00:00

  • Genetic analysis of Leishmania donovani tropism using a naturally attenuated cutaneous strain.

    abstract::A central question in Leishmania research is why most species cause cutaneous infections but others cause fatal visceral disease. Interestingly, L. donovani causes both visceral and cutaneous leishmaniasis in Sri Lanka. L. donovani clinical isolates were therefore obtained from cutaneous leishmaniasis (CL-SL) and visc...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004244

    authors: Zhang WW,Ramasamy G,McCall LI,Haydock A,Ranasinghe S,Abeygunasekara P,Sirimanna G,Wickremasinghe R,Myler P,Matlashewski G

    更新日期:2014-07-03 00:00:00

  • Burkholderia type VI secretion systems have distinct roles in eukaryotic and bacterial cell interactions.

    abstract::Bacteria that live in the environment have evolved pathways specialized to defend against eukaryotic organisms or other bacteria. In this manuscript, we systematically examined the role of the five type VI secretion systems (T6SSs) of Burkholderia thailandensis (B. thai) in eukaryotic and bacterial cell interactions. ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001068

    authors: Schwarz S,West TE,Boyer F,Chiang WC,Carl MA,Hood RD,Rohmer L,Tolker-Nielsen T,Skerrett SJ,Mougous JD

    更新日期:2010-08-26 00:00:00

  • Iron acquisition in Bacillus cereus: the roles of IlsA and bacillibactin in exogenous ferritin iron mobilization.

    abstract::In host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acq...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003935

    authors: Segond D,Abi Khalil E,Buisson C,Daou N,Kallassy M,Lereclus D,Arosio P,Bou-Abdallah F,Nielsen Le Roux C

    更新日期:2014-02-13 00:00:00

  • Inhibition of JNK signaling in the Asian malaria vector Anopheles stephensi extends mosquito longevity and improves resistance to Plasmodium falciparum infection.

    abstract::Malaria is a global health concern caused by infection with Plasmodium parasites. With rising insecticide and drug resistance, there is a critical need to develop novel control strategies, including strategies to block parasite sporogony in key mosquito vector species. MAPK signaling pathways regulated by extracellula...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007418

    authors: Souvannaseng L,Hun LV,Baker H,Klyver JM,Wang B,Pakpour N,Bridgewater JM,Napoli E,Giulivi C,Riehle MA,Luckhart S

    更新日期:2018-11-29 00:00:00

  • Hepatitis B virus core protein phosphorylation: Identification of the SRPK1 target sites and impact of their occupancy on RNA binding and capsid structure.

    abstract::Hepatitis B virus (HBV) replicates its 3 kb DNA genome through capsid-internal reverse transcription, initiated by assembly of 120 core protein (HBc) dimers around a complex of viral pregenomic (pg) RNA and polymerase. Following synthesis of relaxed circular (RC) DNA capsids can be enveloped and secreted as stable vir...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007488

    authors: Heger-Stevic J,Zimmermann P,Lecoq L,Böttcher B,Nassal M

    更新日期:2018-12-19 00:00:00

  • Kinetics of myeloid dendritic cell trafficking and activation: impact on progressive, nonprogressive and controlled SIV infections.

    abstract::We assessed the role of myeloid dendritic cells (mDCs) in the outcome of SIV infection by comparing and contrasting their frequency, mobilization, phenotype, cytokine production and apoptosis in pathogenic (pigtailed macaques, PTMs), nonpathogenic (African green monkeys, AGMs) and controlled (rhesus macaques, RMs) SIV...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003600

    authors: Wijewardana V,Kristoff J,Xu C,Ma D,Haret-Richter G,Stock JL,Policicchio BB,Mobley AD,Nusbaum R,Aamer H,Trichel A,Ribeiro RM,Apetrei C,Pandrea I

    更新日期:2013-01-01 00:00:00

  • Cryo-EM structures reveal two distinct conformational states in a picornavirus cell entry intermediate.

    abstract::The virions of enteroviruses such as poliovirus undergo a global conformational change after binding to the cellular receptor, characterized by a 4% expansion, and by the opening of holes at the two and quasi-three-fold symmetry axes of the capsid. The resultant particle is called a 135S particle or A-particle and is ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008920

    authors: Shah PNM,Filman DJ,Karunatilaka KS,Hesketh EL,Groppelli E,Strauss M,Hogle JM

    更新日期:2020-09-30 00:00:00

  • Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study.

    abstract::Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [P...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003211

    authors: Sáez-Cirión A,Bacchus C,Hocqueloux L,Avettand-Fenoel V,Girault I,Lecuroux C,Potard V,Versmisse P,Melard A,Prazuck T,Descours B,Guergnon J,Viard JP,Boufassa F,Lambotte O,Goujard C,Meyer L,Costagliola D,Venet A,Pancin

    更新日期:2013-03-01 00:00:00

  • Inhibition of IL-10 production by maternal antibodies against Group B Streptococcus GAPDH confers immunity to offspring by favoring neutrophil recruitment.

    abstract::Group B Streptococcus (GBS) is the leading cause of neonatal pneumonia, septicemia, and meningitis. We have previously shown that in adult mice GBS glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extracellular virulence factor that induces production of the immunosuppressive cytokine interleuk...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002363

    authors: Madureira P,Andrade EB,Gama B,Oliveira L,Moreira S,Ribeiro A,Correia-Neves M,Trieu-Cuot P,Vilanova M,Ferreira P

    更新日期:2011-11-01 00:00:00

  • The amino-terminus of the hepatitis C virus (HCV) p7 viroporin and its cleavage from glycoprotein E2-p7 precursor determine specific infectivity and secretion levels of HCV particle types.

    abstract::Viroporins are small transmembrane proteins with ion channel activities modulating properties of intracellular membranes that have diverse proviral functions. Hepatitis C virus (HCV) encodes a viroporin, p7, acting during assembly, envelopment and secretion of viral particles (VP). HCV p7 is released from the viral po...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006774

    authors: Denolly S,Mialon C,Bourlet T,Amirache F,Penin F,Lindenbach B,Boson B,Cosset FL

    更新日期:2017-12-18 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

  • Transfer of Immunity from Mother to Offspring Is Mediated via Egg-Yolk Protein Vitellogenin.

    abstract::Insect immune systems can recognize specific pathogens and prime offspring immunity. High specificity of immune priming can be achieved when insect females transfer immune elicitors into developing oocytes. The molecular mechanism behind this transfer has been a mystery. Here, we establish that the egg-yolk protein vi...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005015

    authors: Salmela H,Amdam GV,Freitak D

    更新日期:2015-07-31 00:00:00

  • Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence.

    abstract::Lymph nodes (LN) and their resident T follicular helper CD4+ T cells (Tfh) are a critical site for HIV replication and persistence. Therefore, optimizing antiviral activity in lymphoid tissues will be needed to reduce or eliminate the HIV reservoir. In this study, we retained effector immune cells in LN of cART-suppre...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008081

    authors: Pino M,Paganini S,Deleage C,Padhan K,Harper JL,King CT,Micci L,Cervasi B,Mudd JC,Gill KP,Jean SM,Easley K,Silvestri G,Estes JD,Petrovas C,Lederman MM,Paiardini M

    更新日期:2019-10-18 00:00:00

  • THY-1 Cell Surface Antigen (CD90) Has an Important Role in the Initial Stage of Human Cytomegalovirus Infection.

    abstract::Human cytomegalovirus (HCMV) infects about 50% of the US population, is the leading infectious cause of birth defects, and is considered the most important infectious agent in transplant recipients. The virus infects many cell types in vivo and in vitro. While previous studies have identified several cellular proteins...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004999

    authors: Li Q,Wilkie AR,Weller M,Liu X,Cohen JI

    更新日期:2015-07-06 00:00:00

  • FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure.

    abstract::Exposure to Plasmodium falciparum is associated with circulating "atypical" memory B cells (atMBCs), which appear similar to dysfunctional B cells found in HIV-infected individuals. Functional analysis of atMBCs has been limited, with one report suggesting these cells are not dysfunctional but produce protective antib...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004894

    authors: Sullivan RT,Kim CC,Fontana MF,Feeney ME,Jagannathan P,Boyle MJ,Drakeley CJ,Ssewanyana I,Nankya F,Mayanja-Kizza H,Dorsey G,Greenhouse B

    更新日期:2015-05-19 00:00:00

  • Nuclear hormone receptor regulation of microRNAs controls innate immune responses in C. elegans.

    abstract::Nuclear hormone receptors respond to small molecules such as retinoids or steroids and regulate development. Signaling in the conserved p38/PMK-1 MAP kinase pathway regulates innate immunity. In this study, we show that the Caenorhabditis elegans nuclear receptor DAF-12 negatively regulates the defense against pathoge...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003545

    authors: Liu F,He CX,Luo LJ,Zou QL,Zhao YX,Saini R,Han SF,Knölker HJ,Wang LS,Ge BX

    更新日期:2013-01-01 00:00:00

  • The mosquito melanization response requires hierarchical activation of non-catalytic clip domain serine protease homologs.

    abstract::Serine protease cascades regulate important insect immune responses namely melanization and Toll pathway activation. An important component of these cascades are clip-domain serine protease homologs (cSPHs), which are non-catalytic, but essential for activating the enzyme prophenoloxidase (PPO) in the melanization res...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008194

    authors: El Moussawi L,Nakhleh J,Kamareddine L,Osta MA

    更新日期:2019-11-25 00:00:00

  • The Cyclase-associated protein Cap1 is important for proper regulation of infection-related morphogenesis in Magnaporthe oryzae.

    abstract::Surface recognition and penetration are critical steps in the infection cycle of many plant pathogenic fungi. In Magnaporthe oryzae, cAMP signaling is involved in surface recognition and pathogenesis. Deletion of the MAC1 adenylate cyclase gene affected appressorium formation and plant infection. In this study, we use...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002911

    authors: Zhou X,Zhang H,Li G,Shaw B,Xu JR

    更新日期:2012-09-01 00:00:00

  • Autophagy pathway induced by a plant virus facilitates viral spread and transmission by its insect vector.

    abstract::Many viral pathogens are persistently transmitted by insect vectors and cause agricultural or health problems. Generally, an insect vector can use autophagy as an intrinsic antiviral defense mechanism against viral infection. Whether viruses can evolve to exploit autophagy to promote their transmission by insect vecto...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006727

    authors: Chen Y,Chen Q,Li M,Mao Q,Chen H,Wu W,Jia D,Wei T

    更新日期:2017-11-10 00:00:00

  • EBNA3C augments Pim-1 mediated phosphorylation and degradation of p21 to promote B-cell proliferation.

    abstract::Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, can latently infect the human population. EBV is associated with several types of malignancies originating from lymphoid and epithelial cell types. EBV latent antigen 3C (EBNA3C) is essential for EBV-induced immortalization of B-cells. The Moloney murine leukem...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004304

    authors: Banerjee S,Lu J,Cai Q,Sun Z,Jha HC,Robertson ES

    更新日期:2014-08-14 00:00:00

  • Elevated catalase expression in a fungal pathogen is a double-edged sword of iron.

    abstract::Most fungal pathogens of humans display robust protective oxidative stress responses that contribute to their pathogenicity. The induction of enzymes that detoxify reactive oxygen species (ROS) is an essential component of these responses. We showed previously that ectopic expression of the heme-containing catalase en...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006405

    authors: Pradhan A,Herrero-de-Dios C,Belmonte R,Budge S,Lopez Garcia A,Kolmogorova A,Lee KK,Martin BD,Ribeiro A,Bebes A,Yuecel R,Gow NAR,Munro CA,MacCallum DM,Quinn J,Brown AJP

    更新日期:2017-05-22 00:00:00