Evidence map›Paper›PMID 27612593›Full record

ArticleEBioMedicine2016

Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity.

Todd Bradley, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, Amanda Eaton, Shi-Mao Xia, Robert Parks and 20 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

32 citing papers in PubMed, 40 citations in OpenAlex.

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  16. Topological analysis of the gp41 MPER on lipid bilayers relevant to the metastable HIV-1 envelope prefusion state.Proceedings of the National Academy of Sciences of the United States of America · 2019
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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

30 authors at 9 institutions in 2 countries.

Todd BradleyDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: todd.bradley@duke.edu.
Ashley TramaDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Nancy TumbaNational Institute for Communicable Diseases, Johannesburg 2131, South Africa.
Elin GrayNational Institute for Communicable Diseases, Johannesburg 2131, South Africa.
Xiaozhi LuDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Navid MadaniDana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
Fatemeh JahanbakhshDana-Farber Cancer Institute, Boston, MA 02215, USA.
Amanda EatonDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Shi-Mao XiaDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Robert ParksDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Krissey E LloydDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Laura L SutherlandDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Richard M ScearceDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Cindy M BowmanDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Susan BarnettNovartis Vaccines and Diagnostics, Inc., Cambridge, MA, USA.
Salim S Abdool-KarimCenter for AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban 4013, South Africa; Columbia University, New York, NY 10032, USA.
Scott D BoydStanford University, Palo Alto, CA 94305, USA.
Bruno MelilloUniversity of Pennsylvania, Philadelphia, PA 19104, USA.
Amos B SmithUniversity of Pennsylvania, Philadelphia, PA 19104, USA.
Joseph SodroskiDana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
Thomas B KeplerBoston University, Boston, MA 02118, USA.
S Munir AlamDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Feng GaoDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Mattia BonsignoriDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Hua-Xin LiaoDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
M Anthony MoodyDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
David MontefioriDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Sampa SantraBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Lynn MorrisNational Institute for Communicable Diseases, Johannesburg 2131, South Africa; Center for AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban 4013, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2131, South Africa.
Barton F HaynesDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: barton.haynes@duke.edu.
Duke Medical Center · USNational Institute for Communicable DiseasesDana-Farber Cancer Institute · USHarvard University · USUniversity of Pennsylvania · USBoston University · USCentre for the AIDS Programme of Research in South Africa · ZANovartis (United States) · USPalo Alto University · US

Funding

Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI MCMICHAEL, ANDREW JAMES · 2012 to 2018
$204.7M
Social and Behavioral Sciences CoreP30AI064518 · NIAID · DUKE UNIVERSITY · PI Nwora Lance Okeke · 2005 to 2026
$50.5M
Understanding Envelope Function in HIV-1 Infection: The Design, Synthesis and Validation of Small Molecule HIV-1 Env InhibitorsP01GM056550 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI ABRAMS, CAMERON F · 1997 to 2018
$31.2M
Conformational Landscape of the HIV-1 Envelope GlycoproteinsR01AI124982 · NIAID · DANA-FARBER CANCER INST · PI SODROSKI, JOSEPH G · 2016 to 2025
$6.7M
Single-particle Reconstruction of HIV-1 Envelope Glycoprotein TrimersR01AI093256 · NIAID · DANA-FARBER CANCER INST · PI SODROSKI, JOSEPH G · 2011 to 2015
$2.2M
NIAID NIH HHS P30 AI064518NIAID NIH HHS R01 AI093256NIAID NIH HHS R01 AI124982NIAID NIH HHS UM1 AI100645NIGMS NIH HHS P01 GM056550
6 · The paper itself

Abstract

Most HIV-1 vaccines elicit neutralizing antibodies that are active against highly sensitive (tier-1) viruses or rare cases of vaccine-matched neutralization-resistant (tier-2) viruses, but no vaccine has induced antibodies that can broadly neutralize heterologous tier-2 viruses. In this study, we isolated antibodies from an HIV-1-infected individual that targeted the gp41 membrane-proximal external region (MPER) that may have selected single-residue changes in viral variants in the MPER that resulted in neutralization sensitivity to antibodies targeting distal epitopes on the HIV-1 Env. Similarly, a single change in the MPER in a second virus from another infected-individual also conferred enhanced neutralization sensitivity. These gp41 single-residue changes thus transformed tier-2 viruses into tier-1 viruses that were sensitive to vaccine-elicited tier-1 neutralizing antibodies. These data demonstrate that Env amino acid changes within the MPER bnAb epitope of naturally-selected escape viruses can increase neutralization sensitivity to multiple types of neutralizing antibodies, and underscore the critical importance of the MPER for maintaining the integrity of the tier-2 HIV-1 trimer.

Indexed as

Amino Acid SubstitutionAIDS VaccinesAmino Acid SequenceAnimalsAntibodies, BlockingAntibodies, NeutralizingAntigenic VariationDisease Models, AnimalGene ExpressionHIV-1HIV AntibodiesHIV Envelope Protein gp120HIV Envelope Protein gp41HIV InfectionsHumansImmunizationAIDS VaccinesAntibodies, BlockingAntibodies, NeutralizingHIV AntibodiesHIV Envelope Protein gp120HIV Envelope Protein gp41

Identifiers

PMID27612593
PMCPMC5078591
OpenAlexW2510605969

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.