Eliminating hepatitis B by antagonizing cellular inhibitors of apoptosis.

Abstract:

:We have shown that cellular inhibitor of apoptosis proteins (cIAPs) impair clearance of hepatitis B virus (HBV) infection by preventing TNF-mediated killing/death of infected cells. A key question, with profound therapeutic implications, is whether this finding can be translated to the development of drugs that promote elimination of infected cells. Drug inhibitors of cIAPs were developed as cancer therapeutics to promote TNF-mediated tumor killing. These drugs are also known as Smac mimetics, because they mimic the action of the endogenous protein Smac/Diablo that antagonizes cIAP function. Here, we show using an immunocompetent mouse model of chronic HBV infection that birinapant and other Smac mimetics are able to rapidly reduce serum HBV DNA and serum HBV surface antigen, and they promote the elimination of hepatocytes containing HBV core antigen. The efficacy of Smac mimetics in treating HBV infection is dependent on their chemistry, host CD4(+) T cells, and TNF. Birinapant enhances the ability of entecavir, an antiviral nucleoside analog, to reduce viral DNA production in HBV-infected animals. These results indicate that birinapant and other Smac mimetics may have efficacy in treating HBV infection and perhaps, other intracellular infections.

authors

Ebert G,Allison C,Preston S,Cooney J,Toe JG,Stutz MD,Ojaimi S,Baschuk N,Nachbur U,Torresi J,Silke J,Begley CG,Pellegrini M

doi

10.1073/pnas.1502400112

subject

Has Abstract

pub_date

2015-05-05 00:00:00

pages

5803-8

issue

18

eissn

0027-8424

issn

1091-6490

pii

1502400112

journal_volume

112

pub_type

杂志文章
  • How stereotypes impair women's careers in science.

    abstract::Women outnumber men in undergraduate enrollments, but they are much less likely than men to major in mathematics or science or to choose a profession in these fields. This outcome often is attributed to the effects of negative sex-based stereotypes. We studied the effect of such stereotypes in an experimental market, ...

    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.1314788111

    authors: Reuben E,Sapienza P,Zingales L

    更新日期:2014-03-25 00:00:00

  • Carboxyfullerenes as neuroprotective agents.

    abstract::Two regioisomers with C3 or D3 symmetry of water-soluble carboxylic acid C60 derivatives, containing three malonic acid groups per molecule, were synthesized and found to be equipotent free radical scavengers in solution as assessed by EPR analysis. Both compounds also inhibited the excitotoxic death of cultured corti...

    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.94.17.9434

    authors: Dugan LL,Turetsky DM,Du C,Lobner D,Wheeler M,Almli CR,Shen CK,Luh TY,Choi DW,Lin TS

    更新日期:1997-08-19 00:00:00

  • U94 of human herpesvirus 6 is expressed in latently infected peripheral blood mononuclear cells and blocks viral gene expression in transformed lymphocytes in culture.

    abstract::Human herpesvirus 6 (HHV-6) like other herpesviruses, expresses sequentially immediate early (IE), early, and late genes during lytic infection. Evidence of ability to establish latent infection has not been available, but by analogy with other herpesviruses it could be expected that IE genes that regulate and transac...

    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.95.23.13911

    authors: Rotola A,Ravaioli T,Gonelli A,Dewhurst S,Cassai E,Di Luca D

    更新日期:1998-11-10 00:00:00

  • Ataxia telangiectasia-mutated protein and DNA-dependent protein kinase have complementary V(D)J recombination functions.

    abstract::Antigen receptor variable region exons are assembled during lymphocyte development from variable (V), diversity (D), and joining (J) gene segments. Each germ-line gene segment is flanked by recombination signal sequences (RSs). Recombination-activating gene endonuclease initiates V(D)J recombination by cleaving a pair...

    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.1019293108

    authors: Zha S,Jiang W,Fujiwara Y,Patel H,Goff PH,Brush JW,Dubois RL,Alt FW

    更新日期:2011-02-01 00:00:00

  • Sulfhydryl oxidation down-regulates T-cell signaling and inhibits tyrosine phosphorylation of phospholipase C gamma 1.

    abstract::Early events in both T-cell receptor (CD3)- and CD4-induced signal transduction pathways include tyrosine phosphorylation of protein substrates, the generation of phosphatidylinositol-phosphate breakdown products, and the mobilization of intracellular Ca2+. Oxidative stress in T cells mediated by sulfhydryl-reactive n...

    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.89.1.300

    authors: Kanner SB,Kavanagh TJ,Grossmann A,Hu SL,Bolen JB,Rabinovitch PS,Ledbetter JA

    更新日期:1992-01-01 00:00:00

  • Detection of genes with a potential for suppressing the transformed phenotype associated with activated ras genes.

    abstract::Seven morphologically nontransformed (flat) revertants with reduced tumorigenicity in vivo have been isolated from populations of Kirsten sarcoma virus-transformed NIH 3T3 cells transfected with a cDNA expression library of normal human fibroblasts. Each revertant harbors 1-10 recombinant plasmids per cell and retains...

    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.86.1.162

    authors: Noda M,Kitayama H,Matsuzaki T,Sugimoto Y,Okayama H,Bassin RH,Ikawa Y

    更新日期:1989-01-01 00:00:00

  • TNFalpha induces ABCA1 through NF-kappaB in macrophages and in phagocytes ingesting apoptotic cells.

    abstract::Recent evidence suggests that tumor necrosis factor alpha (TNFalpha) signaling in vascular cells can have antiatherogenic consequences, but the mechanisms are poorly understood. TNFalpha is released by free cholesterol-loaded apoptotic macrophages, and the clearance of these cells by phagocytic macrophages may help to...

    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.0510345103

    authors: Gerbod-Giannone MC,Li Y,Holleboom A,Han S,Hsu LC,Tabas I,Tall AR

    更新日期:2006-02-28 00:00:00

  • The human plakoglobin gene localizes on chromosome 17q21 and is subjected to loss of heterozygosity in breast and ovarian cancers.

    abstract::The gene encoding human plakoglobin was mapped to chromosome 17q12-q22. An intragenic restriction fragment length polymorphism was used to localize the plakoglobin gene distal to locus KRT10 and proximal to the marker D17S858. The plakoglobin gene colocalizes with the polymorphic 17q21 marker UM8 on the same cosmid in...

    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.92.14.6384

    authors: Aberle H,Bierkamp C,Torchard D,Serova O,Wagner T,Natt E,Wirsching J,Heidkämper C,Montagna M,Lynch HT

    更新日期:1995-07-03 00:00:00

  • Histidines, heart of the hydrogen ion channel from influenza A virus: toward an understanding of conductance and proton selectivity.

    abstract::The heart of the H+ conductance mechanism in the homotetrameric M2 H+ channel from influenza A is a set of four histidine side chains. Here, we show that protonation of the third of these imidazoles coincides with acid activation of this transmembrane channel and that, at physiological pH, the channel is closed by two...

    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.0601944103

    authors: Hu J,Fu R,Nishimura K,Zhang L,Zhou HX,Busath DD,Vijayvergiya V,Cross TA

    更新日期:2006-05-02 00:00:00

  • Human and rat mast cell high-affinity immunoglobulin E receptors: characterization of putative alpha-chain gene products.

    abstract::We have cloned and determined the entire nucleotide sequence of cDNAs corresponding to the putative alpha subunits of the human and rat mast cell high-affinity IgE receptors. Both human and rat cDNAs encode an NH2-terminal signal peptide, two immunoglobulin-like extracellular domains (encoded by discrete exons), a hyd...

    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.85.6.1907

    authors: Shimizu A,Tepler I,Benfey PN,Berenstein EH,Siraganian RP,Leder P

    更新日期:1988-03-01 00:00:00

  • Membrane structure and conformational changes of the antibiotic heterodimeric peptide distinctin by solid-state NMR spectroscopy.

    abstract::The heterodimeric antimicrobial peptide distinctin is composed of 2 linear peptide chains of 22- and 25-aa residues that are connected by a single intermolecular S-S bond. This heterodimer has been considered to be a unique example of a previously unrecorded class of bioactive peptides. Here the 2 distinctin chains we...

    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.0905069106

    authors: Resende JM,Moraes CM,Munhoz VH,Aisenbrey C,Verly RM,Bertani P,Cesar A,Piló-Veloso D,Bechinger B

    更新日期:2009-09-29 00:00:00

  • A neurohypophyseal hormone analog with selective oxytocin-like activities and resistance to enzymatic inactivation: an approach to the design of peptide drugs.

    abstract::Stepwise, synthetic alteration of oxytocin, guided by conformational and enzymological considerations, has led to analogs with specifically modified activity profiles and resistance to enzymatic inactivation. General requirements for the design of peptides with therapeutic value are discussed. ...

    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.71.5.1901

    authors: Walter R,Yamanaka T,Sakakibara S

    更新日期:1974-05-01 00:00:00

  • In vitro reconstitution and steady-state analysis of the fatty acid synthase from Escherichia coli.

    abstract::Microbial fatty acid derivatives are emerging as promising alternatives to fossil fuel derived transportation fuels. Among bacterial fatty acid synthases (FAS), the Escherichia coli FAS is perhaps the most well studied, but little is known about its steady-state kinetic behavior. Here we describe the reconstitution of...

    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.1110852108

    authors: Yu X,Liu T,Zhu F,Khosla C

    更新日期:2011-11-15 00:00:00

  • A combinatorial model for the Macdonald polynomials.

    abstract::We introduce a polynomial C(mu)[Z; q, t], depending on a set of variables Z = z(1), z(2),..., a partition mu, and two extra parameters q, t. The definition of C(mu) involves a pair of statistics (maj(sigma, mu), inv(sigma, mu)) on words sigma of positive integers, and the coefficients of the z(i) are manifestly in N[q...

    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.0405567101

    authors: Haglund J

    更新日期:2004-11-16 00:00:00

  • Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion.

    abstract::The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. The coronavirus spike (S) glycoprotein initiates infection by promoting fusion of the viral and cellular membranes through conformational changes that remain largely uncharacte...

    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.1708727114

    authors: Walls AC,Tortorici MA,Snijder J,Xiong X,Bosch BJ,Rey FA,Veesler D

    更新日期:2017-10-17 00:00:00

  • Inferring epigenetic dynamics from kin correlations.

    abstract::Populations of isogenic embryonic stem cells or clonal bacteria often exhibit extensive phenotypic heterogeneity that arises from intrinsic stochastic dynamics of cells. The phenotypic state of a cell can be transmitted epigenetically in cell division, leading to correlations in the states of cells related by descent....

    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.1504407112

    authors: Hormoz S,Desprat N,Shraiman BI

    更新日期:2015-05-05 00:00:00

  • Intracellular membrane flow: reconstitution of transition vesicle formation and function in a cell-free system.

    abstract::Transfer of membrane between endoplasmic reticulum and Golgi apparatus in situ is considered to occur via 60-nm transition vesicles derived from part-rough, part-smooth transition elements of the endoplasmic reticulum. A procedure is described for the isolation of a fraction enriched in these transition elements from ...

    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.84.17.6098

    authors: Nowack DD,Morré DM,Paulik M,Keenan TW,Morré DJ

    更新日期:1987-09-01 00:00:00

  • Oncogenic transformation by the tax gene of human T-cell leukemia virus type I in vitro.

    abstract::Human T-cell leukemia virus type I (HTLV-I) is a causative agent of adult T-cell leukemia (ATL). To elucidate the role of HTLV-I in leukemogenesis, we examined the biological activity of a defective HTLV-I provirus with the env-pX 3' long terminal repeat region cloned from leukemic cells of an ATL patient. Transfectio...

    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.87.3.1071

    authors: Tanaka A,Takahashi C,Yamaoka S,Nosaka T,Maki M,Hatanaka M

    更新日期:1990-02-01 00:00:00

  • RNAs that bind and change the permeability of phospholipid membranes.

    abstract::The RNA world hypothesis presumes that RNA will be competent for varied essential cellular functions. One such indispensable cell function is regulation of membrane permeability. Though this was not a known RNA activity, selection-amplification yielded RNAs that bound phosphatidylcholine:cholesterol liposomes. At leas...

    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.96.19.10649

    authors: Khvorova A,Kwak YG,Tamkun M,Majerfeld I,Yarus M

    更新日期:1999-09-14 00:00:00

  • Deciding fate in adverse times: sporulation and competence in Bacillus subtilis.

    abstract::Bacteria serve as the central arena for understanding how gene networks and proteins process information and control cellular behaviors. Recently, much effort has been devoted to the investigation of specific bacteria gene circuits as functioning modules. The next challenge is the integrative modeling of complex cellu...

    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.0912185106

    authors: Schultz D,Wolynes PG,Ben Jacob E,Onuchic JN

    更新日期:2009-12-15 00:00:00

  • Non-Hermitian doping of epsilon-near-zero media.

    abstract::In solid-state physics, "doping" is a pivotal concept that allows controlling and engineering of the macroscopic electronic and optical properties of materials such as semiconductors by judiciously introducing small concentrations of impurities. Recently, this concept has been translated to two-dimensional photonic sc...

    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.2001125117

    authors: Coppolaro M,Moccia M,Castaldi G,Engheta N,Galdi V

    更新日期:2020-06-23 00:00:00

  • Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice.

    abstract::The association between poor paternal diet, perturbed embryonic development, and adult offspring ill health represents a new focus for the Developmental Origins of Health and Disease hypothesis. However, our understanding of the underlying mechanisms remains ill-defined. We have developed a mouse paternal low-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.1806333115

    authors: Watkins AJ,Dias I,Tsuro H,Allen D,Emes RD,Moreton J,Wilson R,Ingram RJM,Sinclair KD

    更新日期:2018-10-02 00:00:00

  • Extensive mitochondrial diversity within a single Amerindian tribe.

    abstract::Sequencing of a 360-nucleotide segment of the mitochondrial control region for 63 individuals from an Amerindian tribe, the Nuu-Chah-Nulth of the Pacific Northwest, revealed the existence of 28 lineages defined by 26 variable positions. This represents a substantial level of mitochondrial diversity for a small local p...

    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.88.19.8720

    authors: Ward RH,Frazier BL,Dew-Jager K,Pääbo S

    更新日期:1991-10-01 00:00:00

  • Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus.

    abstract::The emergence of bacterial multidrug resistance to antibiotics threatens to cause regression to the preantibiotic era. Here we present the crystal structure of the large ribosomal subunit from Staphylococcus aureus, a versatile Gram-positive aggressive pathogen, and its complexes with the known antibiotics linezolid a...

    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.1517952112

    authors: Eyal Z,Matzov D,Krupkin M,Wekselman I,Paukner S,Zimmerman E,Rozenberg H,Bashan A,Yonath A

    更新日期:2015-10-27 00:00:00

  • Night-vision brain area in migratory songbirds.

    abstract::Twice each year, millions of night-migratory songbirds migrate thousands of kilometers. To find their way, they must process and integrate spatiotemporal information from a variety of cues including the Earth's magnetic field and the night-time starry sky. By using sensory-driven gene expression, we discovered that ni...

    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.0409575102

    authors: Mouritsen H,Feenders G,Liedvogel M,Wada K,Jarvis ED

    更新日期:2005-06-07 00:00:00

  • Single secretory granules of live cells recruit syntaxin-1 and synaptosomal associated protein 25 (SNAP-25) in large copy numbers.

    abstract::Before secretory vesicles undergo exocytosis, they must recruit the proteins syntaxin-1 and synaptosomal associated protein 25 (SNAP-25) in the plasma membrane. GFP-labeled versions of both proteins cluster at sites where secretory granules have docked. Single-particle tracking shows that minority populations of both ...

    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.1014840107

    authors: Knowles MK,Barg S,Wan L,Midorikawa M,Chen X,Almers W

    更新日期:2010-11-30 00:00:00

  • Nuclear dynamics in a fungal chimera.

    abstract::A fungal colony is a syncytium composed of a branched and interconnected network of cells. Chimerism endows colonies with increased virulence and ability to exploit nutritionally complex substrates. Moreover, chimera formation may be a driver for diversification at the species level by allowing lateral gene transfer 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.1220842110

    authors: Roper M,Simonin A,Hickey PC,Leeder A,Glass NL

    更新日期:2013-08-06 00:00:00

  • Extranuclear estrogen receptor-alpha stimulates NeuroD1 binding to the insulin promoter and favors insulin synthesis.

    abstract::Estrogen receptors (ERs) protect pancreatic islet survival in mice through rapid extranuclear actions. ERalpha also enhances insulin synthesis in cultured islets. Whether ERalpha stimulates insulin synthesis in vivo and, if so, through which mechanism(s) remain largely unknown. To address these issues, we generated a ...

    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.0914501107

    authors: Wong WP,Tiano JP,Liu S,Hewitt SC,Le May C,Dalle S,Katzenellenbogen JA,Katzenellenbogen BS,Korach KS,Mauvais-Jarvis F

    更新日期:2010-07-20 00:00:00

  • Id1 restrains myeloid commitment, maintaining the self-renewal capacity of hematopoietic stem cells.

    abstract::Appropriate hematopoietic stem cell (HSC) self-renewal reflects the tight regulation of cell cycle entry and lineage commitment. Here, we show that Id1, a dominant-negative regulator of E protein transcription factors, maintains HSC self-renewal by preserving the undifferentiated state. Id1-deficient HSCs show increas...

    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.0607894104

    authors: Jankovic V,Ciarrocchi A,Boccuni P,DeBlasio T,Benezra R,Nimer SD

    更新日期:2007-01-23 00:00:00

  • Specific binding of erythropoietin to its receptor on responsive mouse erythroleukemia cells.

    abstract::Erythropoietin (Epo) is a glycoprotein factor that specifically regulates the proliferation and differentiation of erythroid progenitor cells. Here we describe the isolation of Epo-responsive mouse erythroleukemia cell line SKT6, the characterization of the specific binding of biologically active 125I-labeled human Ep...

    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.84.12.4126

    authors: Todokoro K,Kanazawa S,Amanuma H,Ikawa Y

    更新日期:1987-06-01 00:00:00