Evidence map›Paper›PMID 30894475›Full record

ArticleJournal of virology2019

Conformational Engineering of HIV-1 Env Based on Mutational Tolerance in the CD4 and PG16 Bound States.

Jeremiah D Heredia, Jihye Park, Hannah Choi, Kevin S Gill, Erik Procko

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 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.4field-weighted citation impact, top 22% 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

16 citing papers in PubMed, 24 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

Jeremiah D HerediaDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Jihye ParkDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Hannah ChoiDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Kevin S GillDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Erik ProckoDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA procko@illinois.edu.ORCID 0000-0002-0028-490X
University of Illinois Urbana-Champaign · US

Funding

Deep mutational scanning of the HIV-1 Env protein and HIV-targeted host chemokine receptorsR01AI129719 · NIAID · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI PROCKO, ERIK · 2017 to 2020
$1.5M
NIAID NIH HHS R01 AI129719
6 · The paper itself

Abstract

HIV-1 infection is initiated by viral Env engaging the host receptor CD4, triggering Env to transition from a "closed" to "open" conformation during the early events of virus-cell membrane fusion. To understand how Env sequence accommodates this conformational change, mutational landscapes decoupled from virus replication were determined for Env from BaL (clade B) and DU422 (clade C) isolates interacting with CD4 or antibody PG16 that preferentially recognizes closed trimers. Sequence features uniquely important to each bound state were identified, including glycosylation and binding sites. Notably, the Env apical domain and trimerization interface are under selective pressure for PG16 binding. Based on this key observation, mutations were found that increase presentation of quaternary epitopes associated with properly conformed trimers when Env is expressed at the plasma membrane. Many mutations reduce electrostatic repulsion at the Env apex and increase PG16 recognition of Env sequences from clades A and B. Other mutations increase hydrophobic packing at the gp120 inner-outer domain interface and were broadly applicable for engineering Env from diverse strains spanning tiers 1, 2, and 3 across clades A, B, C, and BC recombinants. Core mutations predicted to introduce steric strain in the open state show markedly reduced CD4 interactions. Finally, we demonstrate how our methodology can be adapted to interrogate interactions between membrane-associated Env and the matrix domain of Gag. These findings and methods may assist vaccine design.

Indexed as

Antibodies, NeutralizingCD4 AntigensCD4-Positive T-LymphocytesCell Lineenv Gene Products, Human Immunodeficiency VirusEpitopesHIV-1HIV AntibodiesHIV Envelope Protein gp120HIV InfectionsHIV SeropositivityHumansModels, MolecularMutationProtein BindingProtein ConformationAntibodies, NeutralizingCD4 Antigensenv Gene Products, Human Immunodeficiency VirusEpitopesHIV AntibodiesHIV Envelope Protein gp120broadly neutralizing antibodyCD4conformational changedeep mutational scandirected evolutionEnvgp160human immunodeficiency virusprotein engineeringquaternary epitope

Identifiers

PMID30894475
PMCPMC6532070
OpenAlexW2923493950

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.