Cytoplasmic isoforms of Kaposi sarcoma herpesvirus LANA recruit and antagonize the innate immune DNA sensor cGAS.

Abstract:

:The latency-associated nuclear antigen (LANA) of Kaposi sarcoma herpesvirus (KSHV) is mainly localized and functions in the nucleus of latently infected cells, playing a pivotal role in the replication and maintenance of latent viral episomal DNA. In addition, N-terminally truncated cytoplasmic isoforms of LANA, resulting from internal translation initiation, have been reported, but their function is unknown. Using coimmunoprecipitation and MS, we found the cGMP-AMP synthase (cGAS), an innate immune DNA sensor, to be a cellular interaction partner of cytoplasmic LANA isoforms. By directly binding to cGAS, LANA, and particularly, a cytoplasmic isoform, inhibit the cGAS-STING-dependent phosphorylation of TBK1 and IRF3 and thereby antagonize the cGAS-mediated restriction of KSHV lytic replication. We hypothesize that cytoplasmic forms of LANA, whose expression increases during lytic replication, inhibit cGAS to promote the reactivation of the KSHV from latency. This observation points to a novel function of the cytoplasmic isoforms of LANA during lytic replication and extends the function of LANA from its role during latency to the lytic replication cycle.

authors

Zhang G,Chan B,Samarina N,Abere B,Weidner-Glunde M,Buch A,Pich A,Brinkmann MM,Schulz TF

doi

10.1073/pnas.1516812113

subject

Has Abstract

pub_date

2016-02-23 00:00:00

pages

E1034-43

issue

8

eissn

0027-8424

issn

1091-6490

pii

1516812113

journal_volume

113

pub_type

杂志文章
  • Repeat associated small RNAs vary among parents and following hybridization in maize.

    abstract::Small RNAs (sRNAs) are hypothesized to contribute to hybrid vigor because they maintain genome integrity, contribute to genetic diversity, and control gene expression. We used Illumina sequencing to assess how sRNA populations vary between two maize inbred lines (B73 and Mo17) and their hybrid. We sampled sRNAs from t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1202073109

    authors: Barber WT,Zhang W,Win H,Varala KK,Dorweiler JE,Hudson ME,Moose SP

    更新日期:2012-06-26 00:00:00

  • Efficiency wages in an experimental labor market.

    abstract::There has been recent experimental support for efficiency wage theories of the labor market. This short paper initiates the larger process of evaluating the boundary conditions of the gift- exchange phenomenon. In particular, we will see whether behavior consistent with the fair wage-effort hypothesis can emerge and b...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.152449999

    authors: Rigdon ML

    更新日期:2002-10-01 00:00:00

  • Room-temperature single-electron junction.

    abstract::The design, realization, and test performances of an electronic junction based on single-electron phenomena that works in the air at room temperature are hereby reported. The element consists of an electrochemically etched sharp tungsten stylus over whose tip a nanometer-size crystal was synthesized. Langmuir-Blodgett...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.20.10556

    authors: Facci P,Erokhin V,Carrara S,Nicolini C

    更新日期:1996-10-01 00:00:00

  • The core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability.

    abstract::The folding energetics of the mono-N-glycosylated adhesion domain of the human immune cell receptor cluster of differentiation 2 (hCD2ad) were studied systematically to understand the influence of the N-glycan on the folding energy landscape. Fully elaborated N-glycan structures accelerate folding by 4-fold and stabil...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0810318105

    authors: Hanson SR,Culyba EK,Hsu TL,Wong CH,Kelly JW,Powers ET

    更新日期:2009-03-03 00:00:00

  • Crystal structure of an RNA.DNA hybrid reveals intermolecular intercalation: dimer formation by base-pair swapping.

    abstract::An intermolecular intercalation of base pairs was found at the CA step in the I222 crystal structure of the RNA.DNA hybrid, r(CAAAGAAAAG).d(CTTTTCTTTG), which contains two-thirds of the polypurine tract sequence of HIV-1 with a substitution of cytosine for the initial adenine. This sequence crystallized in both P21212...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1533326100

    authors: Han GW,Kopka ML,Langs D,Sawaya MR,Dickerson RE

    更新日期:2003-08-05 00:00:00

  • National burden of disease in India from indoor air pollution.

    abstract::In the last decade, a number of quantitative epidemiological studies of specific diseases have been done in developing countries that for the first time allow estimation of the total burden of disease (mortality and morbidity) attributable to use of solid fuels in adult women and young children, who jointly receive th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.24.13286

    authors: Smith KR

    更新日期:2000-11-21 00:00:00

  • Heterogeneities in the transmission of infectious agents: implications for the design of control programs.

    abstract::From an analysis of the distributions of measures of transmission rates among hosts, we identify an empirical relationship suggesting that, typically, 20% of the host population contributes at least 80% of the net transmission potential, as measured by the basic reproduction number, R0. This is an example of a statist...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.1.338

    authors: Woolhouse ME,Dye C,Etard JF,Smith T,Charlwood JD,Garnett GP,Hagan P,Hii JL,Ndhlovu PD,Quinnell RJ,Watts CH,Chandiwana SK,Anderson RM

    更新日期:1997-01-07 00:00:00

  • Enrichment for RNA molecules that bind a Diels-Alder transition state analog.

    abstract::RNA molecules that bind a transition state analog for a Diels-Alder reaction (Kd = 0.35 +/- 0.05 mM) were isolated from a starting pool of approximately 10(14) sequences by affinity chromatography. After the initial rise and plateau of the amount of RNA that eluted with soluble analog, a step gradient elution was used...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.26.13028

    authors: Morris KN,Tarasow TM,Julin CM,Simons SL,Hilvert D,Gold L

    更新日期:1994-12-20 00:00:00

  • Calcium alters the sensitivity of intact horizontal cells to dopamine antagonists.

    abstract::Horizontal cells of the carp retina possess dopamine receptors linked to adenylate cyclase. Isolated, intact horizontal cells respond to micromolar concentrations of dopamine, whereas nanomolar concentrations of haloperidol, (+)-butaclamol, and flupenthixol block the dopamine response. Preincubation in Ringer's soluti...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.10.3350

    authors: Van Buskirk R,Dowling JE

    更新日期:1982-05-01 00:00:00

  • Farnesylation of lamin B1 is important for retention of nuclear chromatin during neuronal migration.

    abstract::The role of protein farnesylation in lamin A biogenesis and the pathogenesis of progeria has been studied in considerable detail, but the importance of farnesylation for the B-type lamins, lamin B1 and lamin B2, has received little attention. Lamins B1 and B2 are expressed in nearly every cell type from the earliest s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1303916110

    authors: Jung HJ,Nobumori C,Goulbourne CN,Tu Y,Lee JM,Tatar A,Wu D,Yoshinaga Y,de Jong PJ,Coffinier C,Fong LG,Young SG

    更新日期:2013-05-21 00:00:00

  • Oxygen-mediated heterogeneity of apo-low-density lipoprotein.

    abstract::Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower molecular weight polypeptide components, as characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. This protein...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.7.3173

    authors: Schuh J,Fairclough GF Jr,Haschemeyer RH

    更新日期:1978-07-01 00:00:00

  • Rapid de novo generation of defective interfering RNA by cucumber necrosis virus mutants that do not express the 20-kDa nonstructural protein.

    abstract::It is generally believed that serial passage at high multiplicity of infection (moi) is required for the generation of defective interfering (DI) particles. High levels of DI RNAs are found associated with persistent infections initiated with laboratory cultures of cucumber necrosis virus (CNV). Two synthetic CNV tran...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.24.11153

    authors: Rochon DM

    更新日期:1991-12-15 00:00:00

  • Sustained representation of perspectival shape.

    abstract::Arguably the most foundational principle in perception research is that our experience of the world goes beyond the retinal image; we perceive the distal environment itself, not the proximal stimulation it causes. Shape may be the paradigm case of such "unconscious inference": When a coin is rotated in depth, we infer...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2000715117

    authors: Morales J,Bax A,Firestone C

    更新日期:2020-06-30 00:00:00

  • Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria.

    abstract::The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. Here we present a proof of concept for a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. We use temperate phages to deliver a funct...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1500107112

    authors: Yosef I,Manor M,Kiro R,Qimron U

    更新日期:2015-06-09 00:00:00

  • Parasite stress and pathogen avoidance relate to distinct dimensions of political ideology across 30 nations.

    abstract::People who are more avoidant of pathogens are more politically conservative, as are nations with greater parasite stress. In the current research, we test two prominent hypotheses that have been proposed as explanations for these relationships. The first, which is an intragroup account, holds that these relationships ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,多中心研究

    doi:10.1073/pnas.1607398113

    authors: Tybur JM,Inbar Y,Aarøe L,Barclay P,Barlow FK,de Barra M,Becker DV,Borovoi L,Choi I,Choi JA,Consedine NS,Conway A,Conway JR,Conway P,Adoric VC,Demirci DE,Fernández AM,Ferreira DC,Ishii K,Jakšić I,Ji T,van Leeuwen

    更新日期:2016-11-01 00:00:00

  • Molecular cloning of matrin F/G: A DNA binding protein of the nuclear matrix that contains putative zinc finger motifs.

    abstract::We have isolated a 2.7-kilobase rat liver cDNA clone that contains the entire 544-amino acid coding sequence for matrin F/G. This protein has previously been localized to the internal, fibrogranular areas of the nuclear matrix and shown to bind to DNA on nitrocellulose blots. The predicted amino acid sequence from the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.14.6186

    authors: Hakes DJ,Berezney R

    更新日期:1991-07-15 00:00:00

  • Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172.

    abstract::The endogenous cannabinoid anandamide is removed from the synaptic space by a high-affinity transport system present in neurons and astrocytes, which is inhibited by N-(4-hydroxyphenyl)-arachidonamide (AM404). After internalization, anandamide is hydrolyzed by fatty-acid amide hydrolase (FAAH), an intracellular membra...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0400997101

    authors: Fegley D,Kathuria S,Mercier R,Li C,Goutopoulos A,Makriyannis A,Piomelli D

    更新日期:2004-06-08 00:00:00

  • Role of brain allopregnanolone in the plasticity of gamma-aminobutyric acid type A receptor in rat brain during pregnancy and after delivery.

    abstract::The relation between changes in brain and plasma concentrations of neurosteroids and the function and structure of gamma-aminobutyric acid type A (GABAA) receptors in the brain during pregnancy and after delivery was investigated in rats. In contrast with plasma, where all steroids increased in parallel, the kinetics ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.22.13284

    authors: Concas A,Mostallino MC,Porcu P,Follesa P,Barbaccia ML,Trabucchi M,Purdy RH,Grisenti P,Biggio G

    更新日期:1998-10-27 00:00:00

  • Identification of IL-17-producing FOXP3+ regulatory T cells in humans.

    abstract::IL-17-producing CD4(+) T helper (Th17) cells have recently been defined as a unique subset of proinflammatory helper cells whose development depends on signaling initiated by IL-6 and TGF-beta, autocrine activity of IL-21, activation of STAT3, and induction of the orphan nuclear receptor RORgammat. The maintenance, ex...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0900408106

    authors: Voo KS,Wang YH,Santori FR,Boggiano C,Wang YH,Arima K,Bover L,Hanabuchi S,Khalili J,Marinova E,Zheng B,Littman DR,Liu YJ

    更新日期:2009-03-24 00:00:00

  • Proximity of the manganese cluster of photosystem II to the redox-active tyrosine YZ.

    abstract::Electron spin echo electron-nuclear double resonance (ESE-ENDOR) experiments performed on a broad radical electron paramagnetic resonance (EPR) signal observed in photosystem II particles depleted of Ca2+ indicate that this signal arises from the redox-active tyrosine YZ. The tyrosine EPR signal width is increased rel...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.21.9545

    authors: Gilchrist ML Jr,Ball JA,Randall DW,Britt RD

    更新日期:1995-10-10 00:00:00

  • TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8+ T cell exhaustion.

    abstract::T cells expressing chimeric antigen receptors (CAR T cells) have shown impressive therapeutic efficacy against leukemias and lymphomas. However, they have not been as effective against solid tumors because they become hyporesponsive ("exhausted" or "dysfunctional") within the tumor microenvironment, with decreased cyt...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1905675116

    authors: Seo H,Chen J,González-Avalos E,Samaniego-Castruita D,Das A,Wang YH,López-Moyado IF,Georges RO,Zhang W,Onodera A,Wu CJ,Lu LF,Hogan PG,Bhandoola A,Rao A

    更新日期:2019-06-18 00:00:00

  • MgATP activates the beta cell KATP channel by interaction with its SUR1 subunit.

    abstract::ATP-sensitive potassium (KATP) channels in the pancreatic beta cell membrane mediate insulin release in response to elevation of plasma glucose levels. They are open at rest but close in response to glucose metabolism, producing a depolarization that stimulates Ca2+ influx and exocytosis. Metabolic regulation of KATP ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.12.7185

    authors: Gribble FM,Tucker SJ,Haug T,Ashcroft FM

    更新日期:1998-06-09 00:00:00

  • Evidence for circularization of the avian oncornavirus RNA genome during proviral DNA synthesis from studies of reverse transcription in vitro.

    abstract::The RNA-directed DNA polymerase (deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase EC 2.7.7.7) of avian oncornavirus requires a tryptophan tRNA (tRNATrp) primer molecule located close to the 5' end of the viral RNA genome for the initiation of DNA synthesis in vitro. In this communication we demonstrate that...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.73.4.1329

    authors: Collett MS,Faras AJ

    更新日期:1976-04-01 00:00:00

  • gp160, a tissue-specific marker for insulin-activated glucose transport.

    abstract::We have isolated and partially sequenced a M(r) 160,000 glycoprotein whose rate of cycling to and from the adipocyte cell surface is enhanced by insulin in a manner apparently identical to the effect of insulin on GLUT4 cycling. Based on the protein sequence, we have prepared an antipeptide antibody against this prote...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.17.8017

    authors: Kandror KV,Pilch PF

    更新日期:1994-08-16 00:00:00

  • Genetic elimination of dengue vector mosquitoes.

    abstract::An approach based on mosquitoes carrying a conditional dominant lethal gene (release of insects carrying a dominant lethal, RIDL) is being developed to control the transmission of dengue viruses by vector population suppression. A transgenic strain, designated OX3604C, of the major dengue vector, Aedes aegypti, was en...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1019295108

    authors: Wise de Valdez MR,Nimmo D,Betz J,Gong HF,James AA,Alphey L,Black WC 4th

    更新日期:2011-03-22 00:00:00

  • DP-2, a heterodimeric partner of E2F: identification and characterization of DP-2 proteins expressed in vivo.

    abstract::E2F is a heterodimeric transcription factor that regulates the expression of genes at the G1/S boundary and is composed of two related but distinct families of proteins, E2F and DP. E2F/DP heterodimers form complexes with the retinoblastoma (Rb) protein, the Rb-related proteins p107 and p130, and cyclins/cdks in a cel...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.15.7594

    authors: Rogers KT,Higgins PD,Milla MM,Phillips RS,Horowitz JM

    更新日期:1996-07-23 00:00:00

  • Continuous 1.3-million-year record of East African hydroclimate, and implications for patterns of evolution and biodiversity.

    abstract::The transport of moisture in the tropics is a critical process for the global energy budget and on geologic timescales, has markedly influenced continental landscapes, migratory pathways, and biological evolution. Here we present a continuous, first-of-its-kind 1.3-My record of continental hydroclimate and lake-level ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1512864112

    authors: Lyons RP,Scholz CA,Cohen AS,King JW,Brown ET,Ivory SJ,Johnson TC,Deino AL,Reinthal PN,McGlue MM,Blome MW

    更新日期:2015-12-22 00:00:00

  • Sterigmatocystin-DNA interactions: identification of a major adduct formed after metabolic activation in vitro.

    abstract::Sterigmatocystin (ST), a potent hepatocarcinogen, was covalently bound to calf thymus DNA by incubation in the presence of phenobarbital-induced rat liver microsomes. Acid hydrolysis of ST-modified DNA liberated a major guanine-containing adduct, present in DNA at an estimated level of 1 ST residue per 100-150 nucleot...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.1.179

    authors: Essigmann JM,Barker LJ,Fowler KW,Francisco MA,Reinhold VN,Wogan GN

    更新日期:1979-01-01 00:00:00

  • Sequence, tissue distribution, and chromosomal localization of mRNA encoding a human glucose transporter-like protein.

    abstract::cDNA clones encoding a glucose transporter-like protein have been isolated from adult human liver and kidney cDNA libraries by cross-hybridization with the human HepG2/erythrocyte glucose transporter cDNA. Analysis of the sequence of this 524-amino acid glucose transporter-like protein indicates that it has 55.5% iden...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.15.5434

    authors: Fukumoto H,Seino S,Imura H,Seino Y,Eddy RL,Fukushima Y,Byers MG,Shows TB,Bell GI

    更新日期:1988-08-01 00:00:00

  • Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells.

    abstract::Developing tools for investigating the cellular activity of glycans will help to delineate the molecular basis for aberrant glycosylation in pathological processes such as cancer. Metabolic oligosaccharide engineering, which inserts sugar-reporting groups into cellular glycoconjugates, represents a powerful method for...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0611307104

    authors: Hsu TL,Hanson SR,Kishikawa K,Wang SK,Sawa M,Wong CH

    更新日期:2007-02-20 00:00:00