Evidence map›Paper›PMID 31068428›Full record

ArticleJournal of virology2019

eCD4-Ig Limits HIV-1 Escape More Effectively than CD4-Ig or a Broadly Neutralizing Antibody.

Christoph H Fellinger, Matthew R Gardner, Jesse A Weber, Barnett Alfant, Amber S Zhou, Michael Farzan

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

23 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Molecular therapy. Advances · 2026
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  4. Article
  5. In vivo evolution of env in SHIV-AD8Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  6. Article
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  8. Article
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  11. Article
  12. Review
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  14. Review
  15. Article
  16. Review
  17. Nanoparticles presenting clusters of CD4 expose a universal vulnerability of HIV-1 by mimicking target cells.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  18. Review
  19. Article
  20. Review
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

6 authors at 1 institution in 1 country.

Christoph H FellingerDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.
Matthew R GardnerDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.
Jesse A WeberDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.
Barnett AlfantDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.
Amber S ZhouDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.
Michael FarzanDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA mfarzan@scripps.edu.
Scripps Research Institute · US

Funding

Cell and Gene Therapy for HIV CureUM1AI126623 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI JEROME, KEITH R, KIEM, HANS-PETER · 2016 to 2020
$24.2M
Therapeutic Use of an Enhanced Form of CD4-IgR37AI091476 · NIAID · UNIVERSITY OF FLORIDA · PI FARZAN, MICHAEL R. · 2016 to 2025
$9.2M
Optimizing eCD4-Ig for eradication and a functional cureR01AI129868 · NIAID · UNIVERSITY OF FLORIDA · PI FARZAN, MICHAEL R. · 2017 to 2021
$5.2M
NIAID NIH HHS R01 AI129868NIAID NIH HHS R37 AI091476NIAID NIH HHS UM1 AI126623
6 · The paper itself

Abstract

The engineered antibody-like entry inhibitor eCD4-Ig neutralizes every human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus isolate it has been tested against. The exceptional breadth of eCD4-Ig derives from its ability to closely and simultaneously emulate the HIV-1 receptor CD4 and coreceptors, either CCR5 or CXCR4. Here we investigated whether viral escape from eCD4-Ig is more difficult than that from CD4-Ig or the CD4-binding site antibody NIH45-46. We observed that a viral swarm selected with high concentrations of eCD4-Ig was increasingly resistant to but did not fully escape from eCD4-Ig. In contrast, viruses selected under the same conditions with CD4-Ig or NIH45-46 fully escaped from those inhibitors. eCD4-Ig-resistant viruses acquired unique changes in the V2 apex, V3, V4, and CD4-binding regions of the HIV-1 envelope glycoprotein (Env). Most of the alterations did not directly affect neutralization by eCD4-Ig or neutralizing antibodies. However, alteration of Q428 to an arginine or lysine resulted in markedly greater resistance to eCD4-Ig and CD4-Ig, with correspondingly dramatic losses in infectivity and greater sensitivity to a V3 antibody and to serum from an infected individual. Compensatory mutations in the V3 loop (N301D) and in the V2 apex (K171E) partially restored viral fitness without affecting serum or eCD4-Ig sensitivity. Collectively, these data suggest that multiple mutations will be necessary to fully escape eCD4-Ig without loss of viral fitness.

Indexed as

Antibodies, NeutralizingCD4 AntigensHEK293 CellsHIV-1HIV-2HIV AntibodiesHIV Envelope Protein gp120HIV InfectionsHumansAntibodies, NeutralizingCD4 Antigensgp120 protein, Human immunodeficiency virus 1gp120 protein, Human immunodeficiency virus 2HIV AntibodiesHIV Envelope Protein gp120CCR5CD4eCD4-IgHIV-1viral entry

Identifiers

PMID31068428
PMCPMC6600210
OpenAlexW2943884439

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.