Antibody-dependent enhancement of influenza disease promoted by increase in hemagglutinin stem flexibility and virus fusion kinetics.

Abstract:

:Several next-generation (universal) influenza vaccines and broadly neutralizing antibodies (bNAbs) are in clinical development. Some of these mediate inhibitions of virus replication at the postentry stage or use Fc-dependent mechanisms. Nonneutralizing antibodies have the potential to mediate enhancement of viral infection or disease. In the current study, two monoclonal antibodies (MAbs) 72/8 and 69/1, enhanced respiratory disease (ERD) in mice following H3N2 virus challenge by demonstrating increased lung pathology and changes in lung cytokine/chemokine levels. MAb 78/2 caused changes in the lung viral loads in a dose-dependent manner. Both MAbs increased HA sensitivity to trypsin cleavage at a higher pH range, suggesting MAb-induced conformational changes. pHrodo-labeled virus particles' entry and residence time in the endocytic compartment were tracked during infection of Madin-Darby canine kidney (MDCK) cells. Both MAbs reduced H3N2 virus residence time in the endocytic pathway, suggesting faster virus fusion kinetics. Structurally, 78/2 and 69/1 Fabs bound the globular head or base of the head domain of influenza hemagglutinin (HA), respectively, and induced destabilization of the HA stem domain. Together, this study describes Mab-induced destabilization of the influenza HA stem domain, faster kinetics of influenza virus fusion, and ERD in vivo. The in vivo animal model and in vitro assays described could augment preclinical safety evaluation of antibodies and next-generation influenza vaccines that generate antibodies which do not block influenza virus-receptor interaction.

authors

Winarski KL,Tang J,Klenow L,Lee J,Coyle EM,Manischewitz J,Turner HL,Takeda K,Ward AB,Golding H,Khurana S

doi

10.1073/pnas.1821317116

subject

Has Abstract

pub_date

2019-07-23 00:00:00

pages

15194-15199

issue

30

eissn

0027-8424

issn

1091-6490

pii

1821317116

journal_volume

116

pub_type

杂志文章
  • Identification of phylogenetic footprints in primate tumor necrosis factor-alpha promoters.

    abstract::The human tumor necrosis factor-alpha (TNF-alpha) gene encodes a pleiotropic cytokine that plays a critical role in basic immunologic processes. To investigate the TNF-alpha regulatory region in the primate lineage, we isolated TNF-alpha promoters from representative great apes, Old World monkeys, and New World monkey...

    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.97.12.6614

    authors: Leung JY,McKenzie FE,Uglialoro AM,Flores-Villanueva PO,Sorkin BC,Yunis EJ,Hartl DL,Goldfeld AE

    更新日期:2000-06-06 00:00:00

  • Pyruvate ferredoxin oxidoreductase from the hyperthermophilic archaeon, Pyrococcus furiosus, functions as a CoA-dependent pyruvate decarboxylase.

    abstract::Pyruvate ferredoxin oxidoreductase (POR) has been previously purified from the hyperthermophilic archaeon, Pyrococcus furiosus, an organism that grows optimally at 100 degrees C by fermenting carbohydrates and peptides. The enzyme contains thiamine pyrophosphate and catalyzes the oxidative decarboxylation of pyruvate ...

    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.94.18.9608

    authors: Ma K,Hutchins A,Sung SJ,Adams MW

    更新日期:1997-09-02 00:00:00

  • Use of Monte Carlo calculations in the study of microtubule subunit kinetics.

    abstract::GTP-tubulin forms a cap on microtubule ends during aggregation. The bulk of the microtubule is GDP-tubulin. This complicates the usual simple kinetic theory of subunit exchange at microtubule ends to such an extent that Monte Carlo calculations are needed to handle the complications, except in special cases. The Monte...

    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.80.24.7520

    authors: Chen Y,Hill TL

    更新日期:1983-12-01 00:00:00

  • Progressive hearing loss and gradual deterioration of sensory hair bundles in the ears of mice lacking the actin-binding protein Eps8L2.

    abstract::Mechanotransduction in the mammalian auditory system depends on mechanosensitive channels in the hair bundles that project from the apical surface of the sensory hair cells. Individual stereocilia within each bundle contain a core of tightly packed actin filaments, whose length is dynamically regulated during developm...

    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.1304644110

    authors: Furness DN,Johnson SL,Manor U,Rüttiger L,Tocchetti A,Offenhauser N,Olt J,Goodyear RJ,Vijayakumar S,Dai Y,Hackney CM,Franz C,Di Fiore PP,Masetto S,Jones SM,Knipper M,Holley MC,Richardson GP,Kachar B,Marcotti W

    更新日期:2013-08-20 00:00:00

  • Spinal motor neuron protein supersaturation patterns are associated with inclusion body formation in ALS.

    abstract::Amyotrophic lateral sclerosis (ALS) is a heterogeneous degenerative motor neuron disease linked to numerous genetic mutations in apparently unrelated proteins. These proteins, including SOD1, TDP-43, and FUS, are highly aggregation-prone and form a variety of intracellular inclusion bodies that are characteristic of d...

    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.1613854114

    authors: Ciryam P,Lambert-Smith IA,Bean DM,Freer R,Cid F,Tartaglia GG,Saunders DN,Wilson MR,Oliver SG,Morimoto RI,Dobson CM,Vendruscolo M,Favrin G,Yerbury JJ

    更新日期:2017-05-16 00:00:00

  • Predicting crossover generation in DNA shuffling.

    abstract::We introduce a quantitative framework for assessing the generation of crossovers in DNA shuffling experiments. The approach uses free energy calculations and complete sequence information to model the annealing process. Statistics obtained for the annealing events then are combined with a reassembly algorithm to 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.051631498

    authors: Moore GL,Maranas CD,Lutz S,Benkovic SJ

    更新日期:2001-03-13 00:00:00

  • The zinc fingers of the SR-like protein ZRANB2 are single-stranded RNA-binding domains that recognize 5' splice site-like sequences.

    abstract::The alternative splicing of mRNA is a critical process in higher eukaryotes that generates substantial proteomic diversity. Many of the proteins that are essential to this process contain arginine/serine-rich (RS) domains. ZRANB2 is a widely-expressed and highly-conserved RS-domain protein that can regulate alternativ...

    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.0802466106

    authors: Loughlin FE,Mansfield RE,Vaz PM,McGrath AP,Setiyaputra S,Gamsjaeger R,Chen ES,Morris BJ,Guss JM,Mackay JP

    更新日期:2009-04-07 00:00:00

  • Improvement of neurological deficits in 6-hydroxydopamine-lesioned rats after transplantation with allogeneic simian virus 40 large tumor antigen gene-induced immortalized dopamine cells.

    abstract::The replacement of dopamine (DA) by DA neuron transplants in the treatment of advanced Parkinson disease (PD) is a rational approach. Because of limitations associated with fetal tissue transplants, a clone (1RB3AN27) of simian virus 40 large tumor antigen (LTa) gene-induced immortalized DA neurons were used in this 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.95.3.1265

    authors: Clarkson ED,Rosa FG,Edwards-Prasad J,Weiland DA,Witta SE,Freed CR,Prasad KN

    更新日期:1998-02-03 00:00:00

  • Mutation in the tau gene in familial multiple system tauopathy with presenile dementia.

    abstract::Familial multiple system tauopathy with presenile dementia (MSTD) is a neurodegenerative disease with an abundant filamentous tau protein pathology. It belongs to the group of familial frontotemporal dementias with Parkinsonism linked to chromosome 17 (FTDP-17), a major class of inherited dementing disorders whose gen...

    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.95.13.7737

    authors: Spillantini MG,Murrell JR,Goedert M,Farlow MR,Klug A,Ghetti B

    更新日期:1998-06-23 00:00:00

  • Isolation and sequence of complementary DNA encoding human extracellular superoxide dismutase.

    abstract::A complementary DNA (cDNA) clone from a human placenta cDNA library encoding extracellular superoxide dismutase (EC-SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) has been isolated and the nucleotide sequence determined. The cDNA has a very high G+C content. EC-SOD is synthesized with a putative 18-amino acid...

    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.84.18.6340

    authors: Hjalmarsson K,Marklund SL,Engström A,Edlund T

    更新日期:1987-09-01 00:00:00

  • Arg-735 of the 100-kDa subunit a of the yeast V-ATPase is essential for proton translocation.

    abstract::The vacuolar (H(+))-ATPases (V-ATPases) are ATP-dependent proton pumps that acidify intracellular compartments and pump protons across specialized plasma membranes. Proton translocation occurs through the integral V(0) domain, which contains five different subunits (a, d, c, c', and c"). Proton transport is critically...

    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.221291798

    authors: Kawasaki-Nishi S,Nishi T,Forgac M

    更新日期:2001-10-23 00:00:00

  • Genomic analysis of human and mouse TCL1 loci reveals a complex of tightly clustered genes.

    abstract::TCL1 and TCL1b genes on human chromosome 14q23.1 are activated in T cell leukemias by translocations and inversions at 14q32.1, juxtaposing them to regulatory elements of T cell receptor genes. In this report we present the cloning, mapping, and expression analysis of the human and murine TCL1/Tcl1 locus. In addition ...

    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.96.25.14418

    authors: Hallas C,Pekarsky Y,Itoyama T,Varnum J,Bichi R,Rothstein JL,Croce CM

    更新日期:1999-12-07 00:00:00

  • Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex.

    abstract::Here, using further optimized 3D culture that allows highly selective induction and long-term growth of human ES cell (hESC)-derived cortical neuroepithelium, we demonstrate unique aspects of self-organization in human neocorticogenesis. Self-organized cortical tissue spontaneously forms a polarity along the dorsocaud...

    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.1315710110

    authors: Kadoshima T,Sakaguchi H,Nakano T,Soen M,Ando S,Eiraku M,Sasai Y

    更新日期:2013-12-10 00:00:00

  • Phytosulfokine-alpha, a sulfated pentapeptide, stimulates the proliferation of rice cells by means of specific high- and low-affinity binding sites.

    abstract::Peptide growth factors were isolated from conditioned medium derived from rice (Oryza sativa L.) suspension cultures and identified to be a sulfated pentapeptide [H-Tyr(SO3H)-Ile-Tyr(SO3H)-Thr-Gln-OH] and its C-terminal-truncated tetrapeptide [H-Tyr(SO3H)-Ile-Tyr(SO3H)-Thr-OH]. These structures were identical to the 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.94.24.13357

    authors: Matsubayashi Y,Takagi L,Sakagami Y

    更新日期:1997-11-25 00:00:00

  • Molecular cloning and expression of the 32-kDa subunit of human TFIID reveals interactions with VP16 and TFIIB that mediate transcriptional activation.

    abstract::Transcription factor TFIID consists of TATA binding protein (TBP) and at least eight TBP-associated factors (TAFs). As TAFs are required for activated but not basal transcription, we have proposed that TAFs act as coactivators to mediate signals between activators and the basal transcription machinery. Here we report ...

    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.92.13.5788

    authors: Klemm RD,Goodrich JA,Zhou S,Tjian R

    更新日期:1995-06-20 00:00:00

  • The X chromosome is organized into a gene-rich outer rim and an internal core containing silenced nongenic sequences.

    abstract::We investigated whether genes escape X chromosome inactivation by positioning outside of the territory defined by XIST RNA. Results reveal an unanticipated higher order organization of genes and noncoding sequences. All 15 X-linked genes, regardless of activity, position on the border of the XIST RNA territory, which ...

    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.0601069103

    authors: Clemson CM,Hall LL,Byron M,McNeil J,Lawrence JB

    更新日期:2006-05-16 00:00:00

  • Rigid amphipathic fusion inhibitors, small molecule antiviral compounds against enveloped viruses.

    abstract::Antiviral drugs targeting viral proteins often result in prompt selection for resistance. Moreover, the number of viral targets is limited. Novel antiviral targets are therefore needed. The unique characteristics of fusion between virion envelopes and cell membranes may provide such targets. Like all fusing bilayers, ...

    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.1010026107

    authors: St Vincent MR,Colpitts CC,Ustinov AV,Muqadas M,Joyce MA,Barsby NL,Epand RF,Epand RM,Khramyshev SA,Valueva OA,Korshun VA,Tyrrell DL,Schang LM

    更新日期:2010-10-05 00:00:00

  • Gating of the proton-gated ion channel from Gloeobacter violaceus at pH 4 as revealed by X-ray crystallography.

    abstract::Cryoelectron microscopy and X-ray crystallography have recently been used to generate structural models that likely represent the unliganded closed-channel conformation and the fully liganded open-channel conformation of different members of the nicotinic-receptor superfamily. To characterize the structure of the clos...

    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.1313156110

    authors: Gonzalez-Gutierrez G,Cuello LG,Nair SK,Grosman C

    更新日期:2013-11-12 00:00:00

  • Cell-free translation of highly purified adenovirus messenger RNA.

    abstract::Several polypeptides contained in the coat and the core of adenovirus type 2 particles have been identified as virus gene products. They are synthesized in vitro by a cell-free protein-making system programmed by adenovirus type 2 messenger RNA that has been hybridized with and eluted from virus DNA. Fractionation by ...

    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.71.9.3385

    authors: Eron L,Westphal H

    更新日期:1974-09-01 00:00:00

  • N-Nitroso-N-methylurea elicits mammary cancer in resistant and sensitive rat strains.

    abstract::A single intravenous (i.v.) injection of the water-soluble mammary carcinogen N-nitroso-N-methylurea (NMU; 35 mg/kg of body weight) elicited cancer of the breast in young female rats of two strains in the following incidence: Long-Evans strain, 4%; Sprague-Dawley strain, 70%. In sisters of these rats, a set of 5 i.v. ...

    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.78.2.1185

    authors: Huggins CB,Ueda N,Wiessler M

    更新日期:1981-02-01 00:00:00

  • Magneto-orientation of lecithin crystals.

    abstract::For the purpose of clarifying the magneto-orientation mechanism of several biological membrane systems, xylene-suspended thin-layered single crystals of lecithin, which is a major component of membranes, were subjected to magnetic fields of various strengths, and the orientation behavior of the crystals was analyzed. ...

    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.77.12.7232

    authors: Sakurai I,Kawamura Y,Ikegami A,Iwayanagi S

    更新日期:1980-12-01 00:00:00

  • Regeneration of a functional RNA virus genome by recombination between deletion mutants and requirement for cowpea chlorotic mottle virus 3a and coat genes for systemic infection.

    abstract::RNAs 1 and 2 of the tripartite cowpea chlorotic mottle virus (CCMV) genome are sufficient for RNA replication in protoplasts, whereas systemic infection of cowpea plants additionally requires RNA3, which encodes the 3a noncapsid protein and coat protein. By using biologically active CCMV cDNA clones, we find that dele...

    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.87.5.1820

    authors: Allison R,Thompson C,Ahlquist P

    更新日期:1990-03-01 00:00:00

  • Signatures of selection in the human antibody repertoire: Selective sweeps, competing subclones, and neutral drift.

    abstract::Antibodies are created and refined by somatic evolution in B cell populations, which endows the human immune system with the ability to recognize and eliminate diverse pathogens. However, the evolutionary processes that sculpt antibody repertoires remain poorly understood. Here, using an unbiased repertoire-scale appr...

    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.1814213116

    authors: Horns F,Vollmers C,Dekker CL,Quake SR

    更新日期:2019-01-22 00:00:00

  • Insights into the origin of carbonaceous chondrite organics from their triple oxygen isotope composition.

    abstract::Dust grains of organic matter were the main reservoir of C and N in the forming Solar System and are thus considered to be an essential ingredient for the emergence of life. However, the physical environment and the chemical mechanisms at the origin of these organic grains are still highly debated. In this study, we r...

    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.1808101115

    authors: Tartèse R,Chaussidon M,Gurenko A,Delarue F,Robert F

    更新日期:2018-08-21 00:00:00

  • Industrial emissions cause extreme urban ozone diurnal variability.

    abstract::Simulations with a regional chemical transport model show that anthropogenic emissions of volatile organic compounds and nitrogen oxides (NO(x) = NO + NO(2)) lead to a dramatic diurnal variation of surface ozone (O(3)) in Houston, Texas. During the daytime, photochemical oxidation of volatile organic compounds catalyz...

    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.0401484101

    authors: Zhang R,Lei W,Tie X,Hess P

    更新日期:2004-04-27 00:00:00

  • Human cytomegalovirus latency alters the cellular secretome, inducing cluster of differentiation (CD)4+ T-cell migration and suppression of effector function.

    abstract::After primary infection, human cytomegalovirus (HCMV) persists as a life-long latent infection, with host immunosuppression often resulting in clinical reactivation. During lytic infection, major changes in the expression of secreted cellular proteins (the secretome) occur that have profound effects on host-cell inter...

    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.1204836109

    authors: Mason GM,Poole E,Sissons JG,Wills MR,Sinclair JH

    更新日期:2012-09-04 00:00:00

  • Two yeast nuclear pore complex proteins involved in mRNA export form a cytoplasmically oriented subcomplex.

    abstract::We sublocalized the yeast nucleoporin Nup82 to the cytoplasmic side of the nuclear pore complex (NPC) by immunoelectron microscopy. Moreover, by in vitro binding assays we showed that Nup82 interacts with the C-terminal region of Nup159, a yeast nucleoporin that previously was also localized to the cytoplasmic side 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.95.19.11241

    authors: Hurwitz ME,Strambio-de-Castillia C,Blobel G

    更新日期:1998-09-15 00:00:00

  • Anabolic action of parathyroid hormone regulated by the β2-adrenergic receptor.

    abstract::Parathyroid hormone (PTH), the major calcium-regulating hormone, and norepinephrine (NE), the principal neurotransmitter of sympathetic nerves, regulate bone remodeling by activating distinct cell-surface G protein-coupled receptors in osteoblasts: the parathyroid hormone type 1 receptor (PTHR) and the β(2)-adrenergic...

    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.1109036109

    authors: Hanyu R,Wehbi VL,Hayata T,Moriya S,Feinstein TN,Ezura Y,Nagao M,Saita Y,Hemmi H,Notomi T,Nakamoto T,Schipani E,Takeda S,Kaneko K,Kurosawa H,Karsenty G,Kronenberg HM,Vilardaga JP,Noda M

    更新日期:2012-05-08 00:00:00

  • Evidence for role of glycoprotein carbohydrates in membrane transport: specific inhibition by tunicamycin.

    abstract::Using tunicamycin, we have investigated the role of glycoproteins in membrane transport. Tunicamycin is a glucosamine-containing antibiotic that specifically inhibits dolichol pyrophosphate-mediated glycosylation of asparaginyl residues of glycoproteins. Inhibition of protein glycosylation in chick embryo fibroblasts ...

    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.76.2.791

    authors: Olden K,Pratt RM,Jaworski C,Yamada KM

    更新日期:1979-02-01 00:00:00

  • A signal-arrest-release sequence mediates export and control of the phage P1 endolysin.

    abstract::The Lyz endolysin of bacteriophage P1 was found to cause lysis of the host without a holin. Induction of a plasmid-cloned lyz resulted in lysis, and the lytic event could be triggered prematurely by treatments that dissipate the proton-motive force. Instead of requiring a holin, export was mediated by an N-terminal tr...

    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.0400957101

    authors: Xu M,Struck DK,Deaton J,Wang IN,Young R

    更新日期:2004-04-27 00:00:00