De Novo Herpes Simplex Virus VP16 Expression Gates a Dynamic Programmatic Transition and Sets the Latent/Lytic Balance during Acute Infection in Trigeminal Ganglia.

Abstract:

:The life long relationship between herpes simplex virus and its host hinges on the ability of the virus to aggressively replicate in epithelial cells at the site of infection and transport into the nervous system through axons innervating the infection site. Interaction between the virus and the sensory neuron represents a pivot point where largely unknown mechanisms lead to a latent or a lytic infection in the neuron. Regulation at this pivot point is critical for balancing two objectives, efficient widespread seeding of the nervous system and host survival. By combining genetic and in vivo in approaches, our studies reveal that the balance between latent and lytic programs is a process occurring early in the trigeminal ganglion. Unexpectedly, activation of the latent program precedes entry into the lytic program by 12 -14hrs. Importantly, at the individual neuronal level, the lytic program begins as a transition out of this acute stage latent program and this escape from the default latent program is regulated by de novo VP16 expression. Our findings support a model in which regulated de novo VP16 expression in the neuron mediates entry into the lytic cycle during the earliest stages of virus infection in vivo. These findings support the hypothesis that the loose association of VP16 with the viral tegument combined with sensory axon length and transport mechanisms serve to limit arrival of virion associated VP16 into neuronal nuclei favoring latency. Further, our findings point to specialized features of the VP16 promoter that control the de novo expression of VP16 in neurons and this regulation is a key component in setting the balance between lytic and latent infections in the nervous system.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Sawtell NM,Thompson RL

doi

10.1371/journal.ppat.1005877

subject

Has Abstract

pub_date

2016-09-08 00:00:00

pages

e1005877

issue

9

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-16-00867

journal_volume

12

pub_type

杂志文章
  • The Staphylococcus aureus RNome and its commitment to virulence.

    abstract::Staphylococcus aureus is a major human pathogen causing a wide spectrum of nosocomial and community-associated infections with high morbidity and mortality. S. aureus generates a large number of virulence factors whose timing and expression levels are precisely tuned by regulatory proteins and RNAs. The aptitude of ba...

    journal_title:PLoS pathogens

    pub_type: 杂志文章,评审

    doi:10.1371/journal.ppat.1002006

    authors: Felden B,Vandenesch F,Bouloc P,Romby P

    更新日期:2011-03-01 00:00:00

  • Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

    abstract::Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006956

    authors: Peterson CW,Wang J,Deleage C,Reddy S,Kaur J,Polacino P,Reik A,Huang ML,Jerome KR,Hu SL,Holmes MC,Estes JD,Kiem HP

    更新日期:2018-04-19 00:00:00

  • The central role of cAMP in regulating Plasmodium falciparum merozoite invasion of human erythrocytes.

    abstract::All pathogenesis and death associated with Plasmodium falciparum malaria is due to parasite-infected erythrocytes. Invasion of erythrocytes by P. falciparum merozoites requires specific interactions between host receptors and parasite ligands that are localized in apical organelles called micronemes. Here, we identify...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004520

    authors: Dawn A,Singh S,More KR,Siddiqui FA,Pachikara N,Ramdani G,Langsley G,Chitnis CE

    更新日期:2014-12-18 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

  • Replication of an Autonomous Human Parvovirus in Non-dividing Human Airway Epithelium Is Facilitated through the DNA Damage and Repair Pathways.

    abstract::Human bocavirus 1 (HBoV1) belongs to the genus Bocaparvovirus of the Parvoviridae family, and is an emerging human pathogenic respiratory virus. In vitro, HBoV1 infects well-differentiated/polarized primary human airway epithelium (HAE) cultured at an air-liquid interface (HAE-ALI). Although it is well known that auto...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005399

    authors: Deng X,Yan Z,Cheng F,Engelhardt JF,Qiu J

    更新日期:2016-01-14 00:00:00

  • Leishmania mitochondrial peroxiredoxin plays a crucial peroxidase-unrelated role during infection: insight into its novel chaperone activity.

    abstract::Two-cysteine peroxiredoxins are ubiquitous peroxidases that play various functions in cells. In Leishmania and related trypanosomatids, which lack catalase and selenium-glutathione peroxidases, the discovery of this family of enzymes provided the molecular basis for peroxide removal in these organisms. In this report ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002325

    authors: Castro H,Teixeira F,Romao S,Santos M,Cruz T,Flórido M,Appelberg R,Oliveira P,Ferreira-da-Silva F,Tomás AM

    更新日期:2011-10-01 00:00:00

  • Thy1+ NK [corrected] cells from vaccinia virus-primed mice confer protection against vaccinia virus challenge in the absence of adaptive lymphocytes.

    abstract::While immunological memory has long been considered the province of T- and B-lymphocytes, it has recently been reported that innate cell populations are capable of mediating memory responses. We now show that an innate memory immune response is generated in mice following infection with vaccinia virus, a poxvirus for ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002141

    authors: Gillard GO,Bivas-Benita M,Hovav AH,Grandpre LE,Panas MW,Seaman MS,Haynes BF,Letvin NL

    更新日期:2011-08-01 00:00:00

  • A compact viral processing proteinase/ubiquitin hydrolase from the OTU family.

    abstract::Turnip yellow mosaic virus (TYMV)--a member of the alphavirus-like supergroup of viruses--serves as a model system for positive-stranded RNA virus membrane-bound replication. TYMV encodes a precursor replication polyprotein that is processed by the endoproteolytic activity of its internal cysteine proteinase domain (P...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003560

    authors: Lombardi C,Ayach M,Beaurepaire L,Chenon M,Andreani J,Guerois R,Jupin I,Bressanelli S

    更新日期:2013-08-01 00:00:00

  • Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus.

    abstract::The herpesvirus life cycle has two distinct phases: latency and lytic replication. The balance between these two phases is critical for viral pathogenesis. It is believed that cellular signals regulate the switch from latency to lytic replication. To systematically evaluate the cellular signals regulating this reactiv...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0030044

    authors: Yu F,Harada JN,Brown HJ,Deng H,Song MJ,Wu TT,Kato-Stankiewicz J,Nelson CG,Vieira J,Tamanoi F,Chanda SK,Sun R

    更新日期:2007-03-01 00:00:00

  • An antiviral response directed by PKR phosphorylation of the RNA helicase A.

    abstract::The double-stranded RNA-activated protein kinase R (PKR) is a key regulator of the innate immune response. Activation of PKR during viral infection culminates in phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2alpha) to inhibit protein translation. A broad range of regulator...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000311

    authors: Sadler AJ,Latchoumanin O,Hawkes D,Mak J,Williams BR

    更新日期:2009-02-01 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

    doi:10.1371/journal.ppat.1000192

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

    更新日期:2008-10-01 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

  • Parallel exploitation of diverse host nutrients enhances Salmonella virulence.

    abstract::Pathogen access to host nutrients in infected tissues is fundamental for pathogen growth and virulence, disease progression, and infection control. However, our understanding of this crucial process is still rather limited because of experimental and conceptual challenges. Here, we used proteomics, microbial genetics,...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003301

    authors: Steeb B,Claudi B,Burton NA,Tienz P,Schmidt A,Farhan H,Mazé A,Bumann D

    更新日期:2013-01-01 00:00:00

  • 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

  • Crystal structure of HIV-1 gp41 including both fusion peptide and membrane proximal external regions.

    abstract::The HIV-1 envelope glycoprotein (Env) composed of the receptor binding domain gp120 and the fusion protein subunit gp41 catalyzes virus entry and is a major target for therapeutic intervention and for neutralizing antibodies. Env interactions with cellular receptors trigger refolding of gp41, which induces close appos...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000880

    authors: Buzon V,Natrajan G,Schibli D,Campelo F,Kozlov MM,Weissenhorn W

    更新日期:2010-05-06 00:00:00

  • MCMV-mediated inhibition of the pro-apoptotic Bak protein is required for optimal in vivo replication.

    abstract::Successful replication and transmission of large DNA viruses such as the cytomegaloviruses (CMV) family of viruses depends on the ability to interfere with multiple aspects of the host immune response. Apoptosis functions as a host innate defence mechanism against viral infection, and the capacity to interfere with th...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003192

    authors: Fleming P,Kvansakul M,Voigt V,Kile BT,Kluck RM,Huang DC,Degli-Esposti MA,Andoniou CE

    更新日期:2013-02-01 00:00:00

  • HSV-1-induced disruption of transcription termination resembles a cellular stress response but selectively increases chromatin accessibility downstream of genes.

    abstract::Lytic herpes simplex virus 1 (HSV-1) infection triggers disruption of transcription termination (DoTT) of most cellular genes, resulting in extensive intergenic transcription. Similarly, cellular stress responses lead to gene-specific transcription downstream of genes (DoG). In this study, we performed a detailed comp...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006954

    authors: Hennig T,Michalski M,Rutkowski AJ,Djakovic L,Whisnant AW,Friedl MS,Jha BA,Baptista MAP,L'Hernault A,Erhard F,Dölken L,Friedel CC

    更新日期:2018-03-26 00:00:00

  • Immobility in the sedentary plant-parasitic nematode H. glycines is associated with remodeling of neuromuscular tissue.

    abstract::The sedentary plant-parasitic nematodes are considered among the most economically damaging pathogens of plants. Following infection and the establishment of a feeding site, sedentary nematodes become immobile. Loss of mobility is reversed in adult males while females never regain mobility. The structural basis for th...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007198

    authors: Han Z,Thapa S,Reuter-Carlson U,Reed H,Gates M,Lambert KN,Schroeder NE

    更新日期:2018-08-16 00:00:00

  • Tissue Degeneration following Loss of Schistosoma mansoni cbp1 Is Associated with Increased Stem Cell Proliferation and Parasite Death In Vivo.

    abstract::Schistosomiasis is second only to malaria in terms of the global impact among diseases caused by parasites. A striking feature of schistosomes are their ability to thrive in their hosts for decades. We have previously demonstrated that stem cells, called neoblasts, promote homeostatic tissue maintenance in adult schis...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005963

    authors: Collins JN,Collins JJ 3rd

    更新日期:2016-11-03 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

  • Autophagy protein Atg3 is essential for maintaining mitochondrial integrity and for normal intracellular development of Toxoplasma gondii tachyzoites.

    abstract::Autophagy is a cellular process that is highly conserved among eukaryotes and permits the degradation of cellular material. Autophagy is involved in multiple survival-promoting processes. It not only facilitates the maintenance of cell homeostasis by degrading long-lived proteins and damaged organelles, but it also pl...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002416

    authors: Besteiro S,Brooks CF,Striepen B,Dubremetz JF

    更新日期:2011-12-01 00:00:00

  • Timelines of infection and transmission dynamics of H1N1pdm09 in swine.

    abstract::Influenza is a major cause of mortality and morbidity worldwide. Despite numerous studies of the pathogenesis of influenza in humans and animal models the dynamics of infection and transmission in individual hosts remain poorly characterized. In this study, we experimentally modelled transmission using the H1N1pdm09 i...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008628

    authors: Canini L,Holzer B,Morgan S,Dinie Hemmink J,Clark B,sLoLa Dynamics Consortium.,Woolhouse MEJ,Tchilian E,Charleston B

    更新日期:2020-07-24 00:00:00

  • The Epstein Barr virus circRNAome.

    abstract::Our appreciation for the extent of Epstein Barr virus (EBV) transcriptome complexity continues to grow through findings of EBV encoded microRNAs, new long non-coding RNAs as well as the more recent discovery of over a hundred new polyadenylated lytic transcripts. Here we report an additional layer to the EBV transcrip...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007206

    authors: Ungerleider N,Concha M,Lin Z,Roberts C,Wang X,Cao S,Baddoo M,Moss WN,Yu Y,Seddon M,Lehman T,Tibbetts S,Renne R,Dong Y,Flemington EK

    更新日期:2018-08-06 00:00:00

  • A viral genome landscape of RNA polyadenylation from KSHV latent to lytic infection.

    abstract::RNA polyadenylation (pA) is one of the major steps in regulation of gene expression at the posttranscriptional level. In this report, a genome landscape of pA sites of viral transcripts in B lymphocytes with Kaposi sarcoma-associated herpesvirus (KSHV) infection was constructed using a modified PA-seq strategy. We ide...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003749

    authors: Majerciak V,Ni T,Yang W,Meng B,Zhu J,Zheng ZM

    更新日期:2013-01-01 00:00:00

  • Carbomer-based adjuvant elicits CD8 T-cell immunity by inducing a distinct metabolic state in cross-presenting dendritic cells.

    abstract::There is a critical need for adjuvants that can safely elicit potent and durable T cell-based immunity to intracellular pathogens. Here, we report that parenteral vaccination with a carbomer-based adjuvant, Adjuplex (ADJ), stimulated robust CD8 T-cell responses to subunit antigens and afforded effective immunity again...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1009168

    authors: Lee W,Kingstad-Bakke B,Paulson B,Larsen A,Overmyer K,Marinaik CB,Dulli K,Toy R,Vogel G,Mueller KP,Tweed K,Walsh AJ,Russell J,Saha K,Reyes L,Skala MC,Sauer JD,Shayakhmetov DM,Coon J,Roy K,Suresh M

    更新日期:2021-01-14 00:00:00

  • Monomeric nucleoprotein of influenza A virus.

    abstract::Isolated influenza A virus nucleoprotein exists in an equilibrium between monomers and trimers. Samples containing only monomers or only trimers can be stabilized by respectively low and high salt. The trimers bind RNA with high affinity but remain trimmers, whereas the monomers polymerise onto RNA forming nucleoprote...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003275

    authors: Chenavas S,Estrozi LF,Slama-Schwok A,Delmas B,Di Primo C,Baudin F,Li X,Crépin T,Ruigrok RW

    更新日期:2013-03-01 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

  • Transcriptional activation of the adenoviral genome is mediated by capsid protein VI.

    abstract::Gene expression of DNA viruses requires nuclear import of the viral genome. Human Adenoviruses (Ads), like most DNA viruses, encode factors within early transcription units promoting their own gene expression and counteracting cellular antiviral defense mechanisms. The cellular transcriptional repressor Daxx prevents ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002549

    authors: Schreiner S,Martinez R,Groitl P,Rayne F,Vaillant R,Wimmer P,Bossis G,Sternsdorf T,Marcinowski L,Ruzsics Z,Dobner T,Wodrich H

    更新日期:2012-02-01 00:00:00

  • Biased Pol II fidelity contributes to conservation of functional domains in the Potato spindle tuber viroid genome.

    abstract::Accurate calculation of mutation rates for viruses and viroids is necessary for evolutionary studies and to evaluate adaptation potential. However, estimation of in vivo mutation rates is complicated by selection, which leads to loss or proliferation of certain mutations. To minimize this concern, lethal mutations, in...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1009144

    authors: Wu J,Bisaro DM

    更新日期:2020-12-22 00:00:00

  • Rudra interrupts receptor signaling complexes to negatively regulate the IMD pathway.

    abstract::Insects rely primarily on innate immune responses to fight pathogens. In Drosophila, antimicrobial peptides are key contributors to host defense. Antimicrobial peptide gene expression is regulated by the IMD and Toll pathways. Bacterial peptidoglycans trigger these pathways, through recognition by peptidoglycan recogn...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000120

    authors: Aggarwal K,Rus F,Vriesema-Magnuson C,Ertürk-Hasdemir D,Paquette N,Silverman N

    更新日期:2008-08-08 00:00:00