Anti-viral protection conferred by recombinant adenylate cyclase toxins from Bordetella pertussis carrying a CD8+ T cell epitope from lymphocytic choriomeningitis virus.

Abstract:

:The elucidation of the mechanisms of antigen presentation by major histocompatibility complex class I molecules has stimulated the search for nonreplicative vectors that could deliver CD8+ T cell epitopes to the cytosol of antigen-presenting cells to trigger the activation of specific cytotoxic T lymphocytes (CTLs) in vivo. In the present study, we investigated the potential ability of an invasive adenylate cyclase toxin from Bordetella pertussis, carrying a CD8+ T cell epitope from the nucleoprotein of lymphocytic choriomeningitis virus (LCMV), to stimulate protective anti-viral immunity. Mice immunized with this recombinant toxin developed strong CTL responses against LCMV-infected target cells. Moreover, these mice were protected against an intracerebral challenge with a virulent strain of LCMV that killed all nonimmunized mice within 7 days. This protection was abolished after in vivo elimination of CD8+ T cells. A mutant toxin devoid of adenylate cyclase activity (i.e., cAMP synthesizing activity) was constructed by insertion of a dipeptide into the catalytic site of the molecule. This genetically detoxified invasive toxin carrying the LCMV epitope stimulated a strong CTL response against both peptide-coated and virus-infected target cells, and mice immunized with this molecule were fully protected against a lethal intracerebral LCMV challenge. To our knowledge, this study represents the first demonstration that a genetically detoxified bacterial toxin carrying a viral CTL epitope can stimulate efficient protective immunity.

authors

Saron MF,Fayolle C,Sebo P,Ladant D,Ullmann A,Leclerc C

doi

10.1073/pnas.94.7.3314

subject

Has Abstract

pub_date

1997-04-01 00:00:00

pages

3314-9

issue

7

eissn

0027-8424

issn

1091-6490

journal_volume

94

pub_type

杂志文章
  • An HP1-like protein is missing from transcriptionally silent micronuclei of Tetrahymena.

    abstract::We report the identification and cloning of a 28-kDa polypeptide (p28) in Tetrahymena macronuclei that shares several features with the well studied heterochromatin-associated protein HP1 from Drosophila. Notably, like HP1, p28 contains both a chromodomain and a chromoshadow domain. p28 also shares features with linke...

    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.95.23.13624

    authors: Huang H,Wiley EA,Lending CR,Allis CD

    更新日期:1998-11-10 00:00:00

  • Structural flexibility at a major conserved antibody target on hepatitis C virus E2 antigen.

    abstract::Hepatitis C virus (HCV) is a major cause of liver disease, affecting over 2% of the world's population. The HCV envelope glycoproteins E1 and E2 mediate viral entry, with E2 being the main target of neutralizing antibody responses. Structural investigations of E2 have produced templates for vaccine design, including 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.1609780113

    authors: Kong L,Lee DE,Kadam RU,Liu T,Giang E,Nieusma T,Garces F,Tzarum N,Woods VL Jr,Ward AB,Li S,Wilson IA,Law M

    更新日期:2016-11-08 00:00:00

  • Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand.

    abstract::Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system postulated to be a cell-mediated autoimmune disease in which interferon gamma (IFN-gamma) plays an important role. There is increased IFN-gamma secretion in MS, and IFN-gamma administration induces exacerbations of disease. We foun...

    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.94.2.599

    authors: Balashov KE,Smith DR,Khoury SJ,Hafler DA,Weiner HL

    更新日期:1997-01-21 00:00:00

  • Apparent homology of expressed genes from wood-forming tissues of loblolly pine (Pinus taeda L.) with Arabidopsis thaliana.

    abstract::Pinus taeda L. (loblolly pine) and Arabidopsis thaliana differ greatly in form, ecological niche, evolutionary history, and genome size. Arabidopsis is a small, herbaceous, annual dicotyledon, whereas pines are large, long-lived, coniferous forest trees. Such diverse plants might be expected to differ in a large numbe...

    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.1132171100

    authors: Kirst M,Johnson AF,Baucom C,Ulrich E,Hubbard K,Staggs R,Paule C,Retzel E,Whetten R,Sederoff R

    更新日期:2003-06-10 00:00:00

  • The cell-shape protein MreC interacts with extracytoplasmic proteins including cell wall assembly complexes in Caulobacter crescentus.

    abstract::The bacterial actin homolog, MreB, forms helical cables within the cell that are required for maintenance of a rod shape. These helical structures are thought to be involved in the spatial organization of cell wall (peptidoglycan) synthesizing complexes of penicillin-binding proteins (PBPs). Here, we examined the role...

    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.0507937102

    authors: Divakaruni AV,Loo RR,Xie Y,Loo JA,Gober JW

    更新日期:2005-12-20 00:00:00

  • The right incentives enable ocean sustainability successes and provide hope for the future.

    abstract::Healthy ocean ecosystems are needed to sustain people and livelihoods and to achieve the United Nations Sustainable Development Goals. Using the ocean sustainably requires overcoming many formidable challenges: overfishing, climate change, ocean acidification, and pollution. Despite gloomy forecasts, there is reason f...

    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.1604982113

    authors: Lubchenco J,Cerny-Chipman EB,Reimer JN,Levin SA

    更新日期:2016-12-20 00:00:00

  • G1 cell cycle arrest and apoptosis induction by nuclear Smad4/Dpc4: phenotypes reversed by a tumorigenic mutation.

    abstract::The tumor suppressor Smad4/Dpc4 is a transcription activator that binds specific DNA sequences and whose nuclear localization is induced after exposure to type beta transforming growth factor-like cytokines. We explored an inducible system in which Smad4 protein is activated by translocation to the nucleus when cell l...

    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.96.4.1427

    authors: Dai JL,Bansal RK,Kern SE

    更新日期:1999-02-16 00:00:00

  • Disruption of an intersubunit electrostatic bond is a critical step in glycine receptor activation.

    abstract::Proper regulation of neurotransmission requires that ligand-activated ion channels remain closed until agonist binds. How channels then open remains poorly understood. Glycine receptor (GlyR) gating is initiated by agonist binding at interfaces between adjacent subunits in the extracellular domain. Aspartate-97, locat...

    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.1001845107

    authors: Todorovic J,Welsh BT,Bertaccini EJ,Trudell JR,Mihic SJ

    更新日期:2010-04-27 00:00:00

  • Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting.

    abstract::Genetic deletion studies have shown that haploinsufficiency of Delta-like ligand (Dll) 4, a transmembrane ligand for the Notch family of receptors, results in major vascular defects and embryonic lethality. To better define the role of Dll4 during vascular growth and differentiation, we selected the postnatal retina 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.0611206104

    authors: Lobov IB,Renard RA,Papadopoulos N,Gale NW,Thurston G,Yancopoulos GD,Wiegand SJ

    更新日期:2007-02-27 00:00:00

  • Host factor Hfq of Escherichia coli stimulates elongation of poly(A) tails by poly(A) polymerase I.

    abstract::Current evidence suggests that the length of poly(A) tails of bacterial mRNAs result from a competition between poly(A) polymerase and exoribonucleases that attack the 3' ends of RNAs. Here, we show that host factor Hfq is also involved in poly(A) tail metabolism. Inactivation of the hfq gene reduces the length of pol...

    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.040549897

    authors: Hajnsdorf E,Régnier P

    更新日期:2000-02-15 00:00:00

  • Analysis of 81 genes from 64 plastid genomes resolves relationships in angiosperms and identifies genome-scale evolutionary patterns.

    abstract::Angiosperms are the largest and most successful clade of land plants with >250,000 species distributed in nearly every terrestrial habitat. Many phylogenetic studies have been based on DNA sequences of one to several genes, but, despite decades of intensive efforts, relationships among early diverging lineages and sev...

    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.0709121104

    authors: Jansen RK,Cai Z,Raubeson LA,Daniell H,Depamphilis CW,Leebens-Mack J,Müller KF,Guisinger-Bellian M,Haberle RC,Hansen AK,Chumley TW,Lee SB,Peery R,McNeal JR,Kuehl JV,Boore JL

    更新日期:2007-12-04 00:00:00

  • beta-Glucuronidase from Escherichia coli as a gene-fusion marker.

    abstract::We have developed a gene-fusion system based on the Escherichia coli beta-glucuronidase gene (uidA). The uidA gene has been cloned from E. coli K-12 and its entire nucleotide sequence has been determined. beta-Glucuronidase has been purified to homogeneity and characterized. The enzyme has a subunit molecular weight o...

    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.83.22.8447

    authors: Jefferson RA,Burgess SM,Hirsh D

    更新日期:1986-11-01 00:00:00

  • CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer.

    abstract::Nonresolving chronic inflammation at the neoplastic site is consistently associated with promoting tumor progression and poor patient outcomes. However, many aspects behind the mechanisms that establish this tumor-promoting inflammatory microenvironment remain undefined. Using bladder cancer (BC) as a model, we found ...

    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.1424795112

    authors: Cheah MT,Chen JY,Sahoo D,Contreras-Trujillo H,Volkmer AK,Scheeren FA,Volkmer JP,Weissman IL

    更新日期:2015-04-14 00:00:00

  • Interspersion of repetitive and single-copy sequences in nuclear ribonucleic acid of high molecular weight.

    abstract::Nuclear RNA of high molecular weight, approximately 15 to 30 x 10(3) nucleotides long, isolated from rat ascites cells, has been shown previously to contain both middle repetitive and single-copy sequences. However, it was not known whether these sequences were located on separate molecules or whether they were inters...

    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.71.4.1108

    authors: Holmes DS,Bonner J

    更新日期:1974-04-01 00:00:00

  • A cell type-selective apoptosis-inducing small molecule for the treatment of brain cancer.

    abstract::Glioblastoma multiforme (GBM; grade IV astrocytoma) is the most prevalent and aggressive form of primary brain cancer. A subpopulation of multipotent cells termed GBM cancer stem cells (CSCs) play a critical role in tumor initiation, tumor maintenance, metastasis, drug resistance, and recurrence following surgery. Her...

    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.1816626116

    authors: Lucki NC,Villa GR,Vergani N,Bollong MJ,Beyer BA,Lee JW,Anglin JL,Spangenberg SH,Chin EN,Sharma A,Johnson K,Sander PN,Gordon P,Skirboll SL,Wurdak H,Schultz PG,Mischel PS,Lairson LL

    更新日期:2019-03-26 00:00:00

  • Allele-specific control of Ia molecule surface expression and conformation: implications for a general model of Ia structure-function relationships.

    abstract::Sequence polymorphism of class II major histocompatibility complex-encoded molecules (Ia) not only accounts for the allelic variability in Ia structure relevant to T-lymphocyte responses but also seems to result in differential quantitative expression of particular Ia heterodimers. The contributions of different allel...

    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.84.9.2921

    authors: Braunstein NS,Germain RN

    更新日期:1987-05-01 00:00:00

  • Ocean acidification compromises recruitment success of the threatened Caribbean coral Acropora palmata.

    abstract::Ocean acidification (OA) refers to the ongoing decline in oceanic pH resulting from the uptake of atmospheric CO(2). Mounting experimental evidence suggests that OA will have negative consequences for a variety of marine organisms. Whereas the effect of OA on the calcification of adult reef corals is increasingly well...

    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.1007273107

    authors: Albright R,Mason B,Miller M,Langdon C

    更新日期:2010-11-23 00:00:00

  • Free radical functionalization of surfaces to prevent adverse responses to biomedical devices.

    abstract::Immobilizing a protein, that is fully compatible with the patient, on the surface of a biomedical device should make it possible to avoid adverse responses such as inflammation, rejection, or excessive fibrosis. A surface that strongly binds and does not denature the compatible protein is required. Hydrophilic surface...

    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.1103277108

    authors: Bilek MM,Bax DV,Kondyurin A,Yin Y,Nosworthy NJ,Fisher K,Waterhouse A,Weiss AS,dos Remedios CG,McKenzie DR

    更新日期:2011-08-30 00:00:00

  • Engineering antigen-specific primary human NK cells against HER-2 positive carcinomas.

    abstract::NK cells are promising effectors for tumor adoptive immunotherapy, particularly when considering the targeting of MHC class I low or negative tumors. Yet, NK cells cannot respond to many tumors, which is particularly the case for nonhematopoietic tumors such as carcinomas or melanoma even when these cells lose MHC cla...

    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.0804788105

    authors: Kruschinski A,Moosmann A,Poschke I,Norell H,Chmielewski M,Seliger B,Kiessling R,Blankenstein T,Abken H,Charo J

    更新日期:2008-11-11 00:00:00

  • Purification of a manganese-containing protein involved in photosynthetic oxygen evolution and its use in reconstituting an active membrane.

    abstract::Extraction of thylakoid membranes with cholate in the presence of ammonium sulfate inactivated oxygen evolution and liberated a managanese-containing protein. This protein could be combined with preformed liposomes containing the depleted thylakoid membranes to restore 85% of the original oxygen-evolution activity. 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.77.2.957

    authors: Spector M,Winget GD

    更新日期:1980-02-01 00:00:00

  • Multiplexed variation scanning for 1,000 amplicons in hundreds of patients using mismatch repair detection (MRD) on tag arrays.

    abstract::Identification of the genetic basis of common disease may require comprehensive sequence analysis of coding regions and regulatory elements in patients and controls to find genetic effects caused by rare or heterogeneous mutations. In this study, we demonstrate how mismatch repair detection on tag arrays can be applie...

    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.0506677102

    authors: Faham M,Zheng J,Moorhead M,Fakhrai-Rad H,Namsaraev E,Wong K,Wang Z,Chow SG,Lee L,Suyenaga K,Reichert J,Boudreau A,Eberle J,Bruckner C,Jain M,Karlin-Neumann G,Jones HB,Willis TD,Buxbaum JD,Davis RW

    更新日期:2005-10-11 00:00:00

  • Myogenic factors that regulate expression of muscle-specific microRNAs.

    abstract::Since their discovery as key regulators of early animal development, microRNAs now are recognized as widespread regulators of gene expression. Despite their abundance, little is known regarding the regulation of microRNA biogenesis. We show that three highly conserved muscle-specific microRNAs, miR-1, miR-133 and miR-...

    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.0602831103

    authors: Rao PK,Kumar RM,Farkhondeh M,Baskerville S,Lodish HF

    更新日期:2006-06-06 00:00:00

  • Differential TOR activation and cell proliferation in Arabidopsis root and shoot apexes.

    abstract::The developmental plasticity of plants relies on the remarkable ability of the meristems to integrate nutrient and energy availability with environmental signals. Meristems in root and shoot apexes share highly similar molecular players but are spatially separated by soil. Whether and how these two meristematic tissue...

    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.1618782114

    authors: Li X,Cai W,Liu Y,Li H,Fu L,Liu Z,Xu L,Liu H,Xu T,Xiong Y

    更新日期:2017-03-07 00:00:00

  • The axonal attractant Netrin-1 is an angiogenic factor.

    abstract::Blood vessels and nerves often follow parallel trajectories, suggesting that distal targets use common cues that induce vascularization and innervation. Netrins are secreted by the floor plate and attract commissural axons toward the midline of the neural tube. Here, we show that Netrin-1 is also a potent vascular mit...

    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.0405984101

    authors: Park KW,Crouse D,Lee M,Karnik SK,Sorensen LK,Murphy KJ,Kuo CJ,Li DY

    更新日期:2004-11-16 00:00:00

  • Association of the rIIA protein with the bacterial membrane.

    abstract::Cell membrane proteins synthesized after infection of Escherichia coli B with wild-type phage T4 and rIIA mutants were analyzed by dodecyl sulfate-polyacrylamide gel electrophoresis. A protein with an approximate molecular weight of 74,000 is present in membranes isolated from T4r(+)-infected cells, but is not found i...

    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.70.5.1468

    authors: Ennis HL,Kievitt KD

    更新日期:1973-05-01 00:00:00

  • Conformational switching of chiral colloidal rafts regulates raft-raft attractions and repulsions.

    abstract::Membrane-mediated particle interactions depend both on the properties of the particles themselves and the membrane environment in which they are suspended. Experiments have shown that chiral rod-like inclusions dissolved in a colloidal membrane of opposite handedness assemble into colloidal rafts, which are finite-siz...

    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.1900615116

    authors: Miller JM,Joshi C,Sharma P,Baskaran A,Baskaran A,Grason GM,Hagan MF,Dogic Z

    更新日期:2019-08-06 00:00:00

  • Uncoupling of behavioral and autonomic responses after lesions of the primate orbitofrontal cortex.

    abstract::Successful adaptation to changes in an animal's emotional and motivational environment depends on behavioral flexibility accompanied by changes in bodily responses, e.g., autonomic and endocrine, which support the change in behavior. Here, we identify the orbitofrontal cortex (OFC) as pivotal in the flexible regulatio...

    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.0800417105

    authors: Reekie YL,Braesicke K,Man MS,Roberts AC

    更新日期:2008-07-15 00:00:00

  • Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase 1B: a paradigm for inhibitor design.

    abstract::The structure of the catalytically inactive mutant (C215S) of the human protein-tyrosine phosphatase 1B (PTP1B) has been solved to high resolution in two complexes. In the first, crystals were grown in the presence of bis-(para-phosphophenyl) methane (BPPM), a synthetic high-affinity low-molecular weight nonpeptidic 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.94.25.13420

    authors: Puius YA,Zhao Y,Sullivan M,Lawrence DS,Almo SC,Zhang ZY

    更新日期:1997-12-09 00:00:00

  • Characterizing long-range search behavior in Diptera using complex 3D virtual environments.

    abstract::The exemplary search capabilities of flying insects have established them as one of the most diverse taxa on Earth. However, we still lack the fundamental ability to quantify, represent, and predict trajectories under natural contexts to understand search and its applications. For example, flying insects have evolved ...

    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.1912124117

    authors: Kaushik PK,Renz M,Olsson SB

    更新日期:2020-06-02 00:00:00

  • Stimulation of simian virus 40 late gene expression by simian virus 40 tumor antigen.

    abstract::The early simian virus 40 (SV40) gene product, large tumor (T) antigen, is responsible for the initiation of viral DNA replication and the autoregulation of early gene expression through direct protein-DNA interactions. We investigated the role of T antigen in late viral gene expression, independent of its function 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.81.7.2040

    authors: Brady J,Bolen JB,Radonovich M,Salzman N,Khoury G

    更新日期:1984-04-01 00:00:00