The herpes simplex virus-1 transactivator infected cell protein-4 drives VEGF-A dependent neovascularization.


:Herpes simplex virus-1 (HSV-1) causes lifelong infection affecting between 50 and 90% of the global population. In addition to causing dermal lesions, HSV-1 is a leading cause of blindness resulting from recurrent corneal infection. Corneal disease is characterized by loss of corneal immunologic privilege and extensive neovascularization driven by vascular endothelial growth factor-A (VEGF-A). In the current study, we identify HSV-1 infected cells as the dominant source of VEGF-A during acute infection, and VEGF-A transcription did not require TLR signaling or MAP kinase activation. Rather than being an innate response to the pathogen, VEGF-A transcription was directly activated by the HSV-1 encoded immediate early transcription factor, ICP4. ICP4 bound the proximal human VEGF-A promoter and was sufficient to promote transcription. Transcriptional activation also required cis GC-box elements common to the VEGF-A promoter and HSV-1 early genes. Our results suggest that the neovascularization characteristic of ocular HSV-1 disease is a direct result of HSV-1's major transcriptional regulator, ICP4, and similarities between the VEGF-A promoter and those of HSV-1 early genes.


PLoS Pathog


PLoS pathogens


Wuest T,Zheng M,Efstathiou S,Halford WP,Carr DJ




Has Abstract


2011-10-01 00:00:00














  • T follicular helper cells regulate the activation of B lymphocytes and antibody production during Plasmodium vivax infection.

    abstract::Although the importance of humoral immunity to malaria has been established, factors that control antibody production are poorly understood. Follicular helper T cells (Tfh cells) are pivotal for generating high-affinity, long-lived antibody responses. While it has been proposed that expansion of antigen-specific Tfh c...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Figueiredo MM,Costa PAC,Diniz SQ,Henriques PM,Kano FS,Tada MS,Pereira DB,Soares IS,Martins-Filho OA,Jankovic D,Gazzinelli RT,Antonelli LRDV

    更新日期:2017-07-10 00:00:00

  • The achilles heel of the trojan horse model of HIV-1 trans-infection.

    abstract::To ensure their survival, microbial pathogens have evolved diverse strategies to subvert host immune defenses. The human retrovirus HIV-1 has been proposed to hijack the natural endocytic function of dendritic cells (DCs) to infect interacting CD4 T cells in a process termed trans-infection. Although DCs can be direct...

    journal_title:PLoS pathogens

    pub_type: 杂志文章,评审


    authors: Cavrois M,Neidleman J,Greene WC

    更新日期:2008-06-27 00:00:00

  • Magnaporthe oryzae Glycine-Rich Secretion Protein, Rbf1 Critically Participates in Pathogenicity through the Focal Formation of the Biotrophic Interfacial Complex.

    abstract::Magnaporthe oryzae, the fungus causing rice blast disease, should contend with host innate immunity to develop invasive hyphae (IH) within living host cells. However, molecular strategies to establish the biotrophic interactions are largely unknown. Here, we report the biological function of a M. oryzae-specific gene,...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Nishimura T,Mochizuki S,Ishii-Minami N,Fujisawa Y,Kawahara Y,Yoshida Y,Okada K,Ando S,Matsumura H,Terauchi R,Minami E,Nishizawa Y

    更新日期:2016-10-06 00:00:00

  • Mechanisms of pathogenesis, infective dose and virulence in human parasites.

    abstract::The number of pathogens that are required to infect a host, termed infective dose, varies dramatically across pathogen species. It has recently been predicted that infective dose will depend upon the mode of action of the molecules that pathogens use to facilitate their infection. Specifically, pathogens which use loc...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Leggett HC,Cornwallis CK,West SA

    更新日期:2012-02-01 00:00:00

  • A Novel Virus Causes Scale Drop Disease in Lates calcarifer.

    abstract::From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: de Groof A,Guelen L,Deijs M,van der Wal Y,Miyata M,Ng KS,van Grinsven L,Simmelink B,Biermann Y,Grisez L,van Lent J,de Ronde A,Chang SF,Schrier C,van der Hoek L

    更新日期:2015-08-07 00:00:00

  • HIV and mature dendritic cells: Trojan exosomes riding the Trojan horse?

    abstract::Exosomes are secreted cellular vesicles that can induce specific CD4(+) T cell responses in vivo when they interact with competent antigen-presenting cells like mature dendritic cells (mDCs). The Trojan exosome hypothesis proposes that retroviruses can take advantage of the cell-encoded intercellular vesicle traffic a...

    journal_title:PLoS pathogens

    pub_type: 杂志文章,评审


    authors: Izquierdo-Useros N,Naranjo-Gómez M,Erkizia I,Puertas MC,Borràs FE,Blanco J,Martinez-Picado J

    更新日期:2010-03-26 00:00:00

  • The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi.

    abstract::The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR); however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or in...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Hovius JW,Bijlsma MF,van der Windt GJ,Wiersinga WJ,Boukens BJ,Coumou J,Oei A,de Beer R,de Vos AF,van 't Veer C,van Dam AP,Wang P,Fikrig E,Levi MM,Roelofs JJ,van der Poll T

    更新日期:2009-05-01 00:00:00

  • Anaplasma phagocytophilum Ats-1 is imported into host cell mitochondria and interferes with apoptosis induction.

    abstract::Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, infects human neutrophils and inhibits mitochondria-mediated apoptosis. Bacterial factors involved in this process are unknown. In the present study, we screened a genomic DNA library of A. phagocytophilum for effectors of the type IV s...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Niu H,Kozjak-Pavlovic V,Rudel T,Rikihisa Y

    更新日期:2010-02-19 00:00:00

  • Lipopolysaccharide O structure of adherent and invasive Escherichia coli regulates intestinal inflammation via complement C3.

    abstract::Gut dysbiosis associated with intestinal inflammation is characterized by the blooming of particular bacteria such as adherent-invasive E. coli (AIEC). However, the precise mechanisms by which AIEC impact on colitis remain largely unknown. Here we show that antibiotic-induced dysbiosis worsened chemically-induced coli...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Ohno M,Hasegawa M,Hayashi A,Caballero-Flores G,Alteri CJ,Lawley TD,Kamada N,Núñez G,Inohara N

    更新日期:2020-10-07 00:00:00

  • Direct identification of the Meloidogyne incognita secretome reveals proteins with host cell reprogramming potential.

    abstract::The root knot nematode, Meloidogyne incognita, is an obligate parasite that causes significant damage to a broad range of host plants. Infection is associated with secretion of proteins surrounded by proliferating cells. Many parasites are known to secrete effectors that interfere with plant innate immunity, enabling ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Bellafiore S,Shen Z,Rosso MN,Abad P,Shih P,Briggs SP

    更新日期:2008-10-01 00:00:00

  • The Base Excision Repair system of Salmonella enterica serovar typhimurium counteracts DNA damage by host nitric oxide.

    abstract::Intracellular pathogens must withstand nitric oxide (NO.) generated by host phagocytes. Salmonella enterica serovar Typhimurium interferes with intracellular trafficking of inducible nitric oxide synthase (iNOS) and possesses multiple systems to detoxify NO.. Consequently, the level of NO. stress encountered by S. Typ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Richardson AR,Soliven KC,Castor ME,Barnes PD,Libby SJ,Fang FC

    更新日期:2009-05-01 00:00:00

  • Pomalidomide restores immune recognition of primary effusion lymphoma through upregulation of ICAM-1 and B7-2.

    abstract::Pomalidomide (Pom) is an immunomodulatory drug that has efficacy against Kaposi's sarcoma, a tumor caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Pom also induces direct cytotoxicity in primary effusion lymphoma (PEL), a B-cell malignancy caused by KSHV, in part through downregulation of IRF4, cMyc, and CK1...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Shrestha P,Davis DA,Jaeger HK,Stream A,Aisabor AI,Yarchoan R

    更新日期:2021-01-07 00:00:00

  • A type VII secretion system of Streptococcus gallolyticus subsp. gallolyticus contributes to gut colonization and the development of colon tumors.

    abstract::Streptococcus gallolyticus subspecies gallolyticus (Sgg) has a strong clinical association with colorectal cancer (CRC) and actively promotes the development of colon tumors. However, the molecular determinants involved in Sgg pathogenicity in the gut are unknown. Bacterial type VII secretion systems (T7SS) mediate pa...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Taylor JC,Gao X,Xu J,Holder M,Petrosino J,Kumar R,Liu W,Höök M,Mackenzie C,Hillhouse A,Brashear W,Nunez MP,Xu Y

    更新日期:2021-01-06 00:00:00

  • TLR3 signaling in macrophages is indispensable for the protective immunity of invariant natural killer T cells against enterovirus 71 infection.

    abstract::Enterovirus 71 (EV71) is the most virulent pathogen among enteroviruses that cause hand, foot and mouth disease in children but rarely in adults. The mechanisms that determine the age-dependent susceptibility remain largely unclear. Here, we found that the paucity of invariant natural killer T (iNKT) cells together wi...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Zhu K,Yang J,Luo K,Yang C,Zhang N,Xu R,Chen J,Jin M,Xu B,Guo N,Wang J,Chen Z,Cui Y,Zhao H,Wang Y,Deng C,Bai L,Ge B,Qin CF,Shen H,Yang CF,Leng Q

    更新日期:2015-01-23 00:00:00

  • Uropathogenic Escherichia coli P and Type 1 fimbriae act in synergy in a living host to facilitate renal colonization leading to nephron obstruction.

    abstract::The progression of a natural bacterial infection is a dynamic process influenced by the physiological characteristics of the target organ. Recent developments in live animal imaging allow for the study of the dynamic microbe-host interplay in real-time as the infection progresses within an organ of a live host. Here w...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Melican K,Sandoval RM,Kader A,Josefsson L,Tanner GA,Molitoris BA,Richter-Dahlfors A

    更新日期:2011-02-01 00:00:00

  • Differential contribution of PB1-F2 to the virulence of highly pathogenic H5N1 influenza A virus in mammalian and avian species.

    abstract::Highly pathogenic avian influenza A viruses (HPAIV) of the H5N1 subtype occasionally transmit from birds to humans and can cause severe systemic infections in both hosts. PB1-F2 is an alternative translation product of the viral PB1 segment that was initially characterized as a pro-apoptotic mitochondrial viral pathog...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Schmolke M,Manicassamy B,Pena L,Sutton T,Hai R,Varga ZT,Hale BG,Steel J,Pérez DR,García-Sastre A

    更新日期:2011-08-01 00:00:00

  • The role of host DNA ligases in hepadnavirus covalently closed circular DNA formation.

    abstract::Hepadnavirus covalently closed circular (ccc) DNA is the bona fide viral transcription template, which plays a pivotal role in viral infection and persistence. Upon infection, the non-replicative cccDNA is converted from the incoming and de novo synthesized viral genomic relaxed circular (rc) DNA, presumably through e...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Long Q,Yan R,Hu J,Cai D,Mitra B,Kim ES,Marchetti A,Zhang H,Wang S,Liu Y,Huang A,Guo H

    更新日期:2017-12-29 00:00:00

  • 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...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    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

    更新日期:2018-12-10 00:00:00

  • Epstein-Barr virus LMP1 manipulates the content and functions of extracellular vesicles to enhance metastatic potential of recipient cells.

    abstract::Extracellular vesicles (EV) mediate intercellular communication events and alterations in normal vesicle content contribute to function and disease initiation or progression. The ability to package a variety of cargo and transmit molecular information between cells renders EVs important mediators of cell-to-cell cross...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Nkosi D,Sun L,Duke LC,Meckes DG Jr

    更新日期:2020-12-31 00:00:00

  • Vaccinia virus E3 protein prevents the antiviral action of ISG15.

    abstract::The ubiquitin-like modifier ISG15 is one of the most predominant proteins induced by type I interferons (IFN). In this study, murine embryo fibroblast (MEFs) and mice lacking the gene were used to demonstrate a novel role of ISG15 as a host defense molecule against vaccinia virus (VACV) infection. In MEFs, the growth ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Guerra S,Cáceres A,Knobeloch KP,Horak I,Esteban M

    更新日期:2008-07-04 00:00:00

  • Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.

    abstract::Cellular responses to Plasmodium falciparum parasites, in particular interferon-gamma (IFNγ) production, play an important role in anti-malarial immunity. However, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation to exposure are difficul...

    journal_title:PLoS pathogens

    pub_type: 临床试验,杂志文章


    authors: Teirlinck AC,McCall MB,Roestenberg M,Scholzen A,Woestenenk R,de Mast Q,van der Ven AJ,Hermsen CC,Luty AJ,Sauerwein RW

    更新日期:2011-12-01 00:00:00

  • Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages.

    abstract::Mycobacterial infection leads to activation of the RIG-I/MAVS/TBK1 RNA sensing pathway in macrophages but the consequences of this activation remains poorly defined. In this study, we determined that activation of this RNA sensing pathway stimulates ICAM-1 expression in M.avium-infected macrophage through the inhibiti...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Cheng Y,Kiene NJ,Tatarian A,Eix EF,Schorey JS

    更新日期:2020-05-28 00:00:00

  • Red-light is an environmental effector for mutualism between begomovirus and its vector whitefly.

    abstract::Environments such as light condition influence the spread of infectious diseases by affecting insect vector behavior. However, whether and how light affects the host defense which further affects insect preference and performance, remains unclear, nor has been demonstrated how pathogens co-adapt light condition to fac...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Zhao P,Zhang X,Gong Y,Wang D,Xu D,Wang N,Sun Y,Gao L,Liu SS,Deng XW,Kliebenstein DJ,Zhou X,Fang RX,Ye J

    更新日期:2021-01-11 00:00:00

  • Membrane alterations induced by nonstructural proteins of human norovirus.

    abstract::Human noroviruses (huNoV) are the most frequent cause of non-bacterial acute gastroenteritis worldwide, particularly genogroup II genotype 4 (GII.4) variants. The viral nonstructural (NS) proteins encoded by the ORF1 polyprotein induce vesical clusters harboring the viral replication sites. Little is known so far abou...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Doerflinger SY,Cortese M,Romero-Brey I,Menne Z,Tubiana T,Schenk C,White PA,Bartenschlager R,Bressanelli S,Hansman GS,Lohmann V

    更新日期:2017-10-27 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


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

    更新日期:2016-10-06 00:00:00

  • Association of host protein VARICOSE with HCPro within a multiprotein complex is crucial for RNA silencing suppression, translation, encapsidation and systemic spread of potato virus A infection.

    abstract::In this study, we investigated the significance of a conserved five-amino acid motif 'AELPR' in the C-terminal region of helper component-proteinase (HCPro) for potato virus A (PVA; genus Potyvirus) infection. This motif is a putative interaction site for WD40 domain-containing proteins, including VARICOSE (VCS). We a...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: De S,Pollari M,Varjosalo M,Mäkinen K

    更新日期:2020-10-12 00:00:00

  • RIG-I-like receptor activation drives type I IFN and antiviral signaling to limit Hantaan orthohantavirus replication.

    abstract::Pathogenic hantaviruses, genus Orthohantaviridae, are maintained in rodent reservoirs with zoonotic transmission to humans occurring through inhalation of rodent excreta. Hantavirus disease in humans is characterized by localized vascular leakage and elevated levels of circulating proinflammatory cytokines. Despite th...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Kell AM,Hemann EA,Turnbull JB,Gale M Jr

    更新日期:2020-04-24 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


    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

  • Overcoming antigenic diversity by enhancing the immunogenicity of conserved epitopes on the malaria vaccine candidate apical membrane antigen-1.

    abstract::Malaria vaccine candidate Apical Membrane Antigen-1 (AMA1) induces protection, but only against parasite strains that are closely related to the vaccine. Overcoming the AMA1 diversity problem will require an understanding of the structural basis of cross-strain invasion inhibition. A vaccine containing four diverse al...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Dutta S,Dlugosz LS,Drew DR,Ge X,Ababacar D,Rovira YI,Moch JK,Shi M,Long CA,Foley M,Beeson JG,Anders RF,Miura K,Haynes JD,Batchelor AH

    更新日期:2013-01-01 00:00:00

  • Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes.

    abstract::Mycobacterium tuberculosis is sensitive to nitric oxide generated by inducible nitric oxide synthase (iNOS). Consequently, to ensure its survival in macrophages, M. tuberculosis inhibits iNOS recruitment to its phagosome by an unknown mechanism. Here we report the mechanism underlying this process, whereby mycobacteri...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Davis AS,Vergne I,Master SS,Kyei GB,Chua J,Deretic V

    更新日期:2007-12-01 00:00:00