Evidence map›Paper›PMID 26485028›Full record

ArticlePLoS pathogens2015

Antigenic Characterization of the HCMV gH/gL/gO and Pentamer Cell Entry Complexes Reveals Binding Sites for Potently Neutralizing Human Antibodies.

Claudio Ciferri, Sumana Chandramouli, Alexander Leitner, Danilo Donnarumma, Michael A Cianfrocco, Rachel Gerrein, Kristian Friedrich, Yukti Aggarwal, Giuseppe Palladino, Ruedi Aebersold and 3 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
7.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
  2. Article
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  4. The Pentamer glycoprotein complex inhibits viral Immediate Early transcription during Human Cytomegalovirus infections.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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  19. The structural basis of herpesvirus entry.Nature reviews. Microbiology · 2021
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 3 countries.

Claudio CiferriNovartis Vaccines (a GSK company), Cambridge, Massachusetts, United States of America.
Sumana ChandramouliNovartis Vaccines (a GSK company), Cambridge, Massachusetts, United States of America.
Alexander LeitnerETH Zürich, Department of Biology, Institute of Molecular Systems Biology, Zürich, Switzerland.
Danilo DonnarummaNovartis Vaccines (a GSK company), Siena, Italy.
Michael A CianfroccoHarvard University, Department of Molecular and Cellular Biology, Cambridge, Massachusetts, United States of America; Harvard Medical School, Department of Cell Biology, Boston, Massachusetts, United States of America.
Rachel GerreinNovartis Vaccines (a GSK company), Cambridge, Massachusetts, United States of America.
Kristian FriedrichNovartis Vaccines (a GSK company), Cambridge, Massachusetts, United States of America.
Yukti AggarwalNovartis Vaccines (a GSK company), Cambridge, Massachusetts, United States of America.
Giuseppe PalladinoNovartis Vaccines (a GSK company), Cambridge, Massachusetts, United States of America.
Ruedi AebersoldETH Zürich, Department of Biology, Institute of Molecular Systems Biology, Zürich, Switzerland; Faculty of Science, University of Zurich, Zurich, Switzerland.
Nathalie NoraisNovartis Vaccines (a GSK company), Siena, Italy.
Ethan C SettembreNovartis Vaccines (a GSK company), Cambridge, Massachusetts, United States of America.
Andrea CarfiNovartis Vaccines (a GSK company), Cambridge, Massachusetts, United States of America.
Novartis (United States) · USNovartis (Italy) · ITETH Zurich · CHHarvard University · USUniversity of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human Cytomegalovirus (HCMV) is a major cause of morbidity and mortality in transplant patients and in fetuses following congenital infection. The glycoprotein complexes gH/gL/gO and gH/gL/UL128/UL130/UL131A (Pentamer) are required for HCMV entry in fibroblasts and endothelial/epithelial cells, respectively, and are targeted by potently neutralizing antibodies in the infected host. Using purified soluble forms of gH/gL/gO and Pentamer as well as a panel of naturally elicited human monoclonal antibodies, we determined the location of key neutralizing epitopes on the gH/gL/gO and Pentamer surfaces. Mass Spectrometry (MS) coupled to Chemical Crosslinking or to Hydrogen Deuterium Exchange was used to define residues that are either in proximity or part of neutralizing epitopes on the glycoprotein complexes. We also determined the molecular architecture of the gH/gL/gO- and Pentamer-antibody complexes by Electron Microscopy (EM) and 3D reconstructions. The EM analysis revealed that the Pentamer specific neutralizing antibodies bind to two opposite surfaces of the complex, suggesting that they may neutralize infection by different mechanisms. Together, our data identify the location of neutralizing antibodies binding sites on the gH/gL/gO and Pentamer complexes and provide a framework for the development of antibodies and vaccines against HCMV.

Indexed as

Antibodies, MonoclonalAntibodies, NeutralizingAntigens, ViralBinding SitesCell LineChromatography, LiquidCytomegalovirusEnzyme-Linked Immunosorbent AssayEpitopes, B-LymphocyteHumansSurface Plasmon ResonanceTandem Mass SpectrometryTransfectionViral Fusion ProteinsVirus InternalizationAntibodies, MonoclonalAntibodies, NeutralizingAntigens, ViralEpitopes, B-LymphocyteViral Fusion Proteins

Identifiers

PMID26485028
PMCPMC4617720
OpenAlexW2157752669

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.