Evidence map›Paper›PMID 32745149›Full record

ArticlePLoS pathogens2020

Recognition of a highly conserved glycoprotein B epitope by a bivalent antibody neutralizing HCMV at a post-attachment step.

Xiaohua Ye, Hang Su, Daniel Wrapp, Daniel C Freed, Fengsheng Li, Zihao Yuan, Aimin Tang, Leike Li, Zhiqiang Ku, Wei Xiong and 7 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

18 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Computational design of prefusion-stabilized Herpesvirus gB trimers.bioRxiv : the preprint server for biology · 2024
    Article
  6. Article
  7. Structure-based design of a soluble human cytomegalovirus glycoprotein B antigen stabilized in a prefusion-like conformation.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Protective anti-gB neutralizing antibodies targeting two vulnerable sites for EBV-cell membrane fusion.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  14. Review
  15. Article
  16. Article
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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

17 authors at 5 institutions in 2 countries.

Xiaohua YeTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.ORCID 0000-0002-2300-4739
Hang SuTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.ORCID 0000-0002-8730-3375
Daniel WrappDepartment of Molecular Biosciences, University of Texas at Austin, Austin, Texas, United States of America.ORCID 0000-0002-0538-9647
Daniel C FreedMerck Research Laboratory, Merck & Co., Inc., Kenilworth, New Jersey, United States of America.
Fengsheng LiMerck Research Laboratory, Merck & Co., Inc., Kenilworth, New Jersey, United States of America.
Zihao YuanTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
Aimin TangMerck Research Laboratory, Merck & Co., Inc., Kenilworth, New Jersey, United States of America.
Leike LiTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.ORCID 0000-0002-1379-1396
Zhiqiang KuTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
Wei XiongTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
Dabbu JaijyanDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America.
Hua ZhuDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America.
Dai WangMerck Research Laboratory, Merck & Co., Inc., Kenilworth, New Jersey, United States of America.
Jason S McLellanDepartment of Molecular Biosciences, University of Texas at Austin, Austin, Texas, United States of America.ORCID 0000-0003-3991-542X
Ningyan ZhangTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.ORCID 0000-0002-4348-2180
Tong-Ming FuTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.ORCID 0000-0003-1420-2271
Zhiqiang AnTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.ORCID 0000-0001-9309-2335
Brown Foundation · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USRutgers, The State University of New Jersey · USThe University of Texas at Austin · USShenyang Pharmaceutical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human cytomegalovirus (HCMV) is one of the main causative agents of congenital viral infection in neonates. HCMV infection also causes serious morbidity and mortality among organ transplant patients. Glycoprotein B (gB) is a major target for HCMV neutralizing antibodies, yet the underlying neutralization mechanisms remain largely unknown. Here we report that 3-25, a gB-specific monoclonal antibody previously isolated from a healthy HCMV-positive donor, efficiently neutralized 14 HCMV strains in both ARPE-19 cells and MRC-5 cells. The core epitope of 3-25 was mapped to a highly conserved linear epitope on antigenic domain 2 (AD-2) of gB. A 1.8 Å crystal structure of 3-25 Fab in complex with the peptide epitope revealed the molecular determinants of 3-25 binding to gB at atomic resolution. Negative-staining electron microscopy (EM) 3D reconstruction of 3-25 Fab in complex with de-glycosylated postfusion gB showed that 3-25 Fab fully occupied the gB trimer at the N-terminus with flexible binding angles. Functionally, 3-25 efficiently inhibited HCMV infection at a post-attachment step by interfering with viral membrane fusion, and restricted post-infection viral spreading in ARPE-19 cells. Interestingly, bivalency was required for HCMV neutralization by AD-2 specific antibody 3-25 but not the AD-4 specific antibody LJP538. In contrast, bivalency was not required for HCMV binding by both antibodies. Taken together, our results reveal the structural basis of gB recognition by 3-25 and demonstrate that inhibition of viral membrane fusion and a requirement of bivalency may be common for gB AD-2 specific neutralizing antibody.

Indexed as

Amino Acid MotifsAntibodies, NeutralizingAntibodies, ViralConserved SequenceCytomegalovirusCytomegalovirus InfectionsEpitopesHumansViral Envelope ProteinsVirus InternalizationAntibodies, NeutralizingAntibodies, ViralEpitopesglycoprotein B, SimplexvirusViral Envelope Proteins

Identifiers

PMID32745149
PMCPMC7425986
OpenAlexW3047152264

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.