ArticlePloS one2010
4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Unique genotypic features of HIV-1 C gp41 membrane proximal external region variants during pregnancy relate to mother-to-child transmission via breastfeeding.Journal of clinical pediatrics and neonatology · 2021Article
- An MPER antibody neutralizes HIV-1 using germline features shared among donors.Nature communications · 2019Article
- Breast milk and in utero transmission of HIV-1 select for envelope variants with unique molecular signatures.Retrovirology · 2017Article
- Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity.EBioMedicine · 2016Article
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- A High Throughput Protein Microarray Approach to Classify HIV Monoclonal Antibodies and Variant Antigens.PloS one · 2015Article
- Drift of the HIV-1 envelope glycoprotein gp120 toward increased neutralization resistance over the course of the epidemic: a comprehensive study using the most potent and broadly neutralizing monoclonal antibodies.Journal of virology · 2014Article
- Antibody to gp41 MPER alters functional properties of HIV-1 Env without complete neutralization.PLoS pathogens · 2014Article
- Article
- Closing the door to human immunodeficiency virus.Protein & cell · 2013Review
- Coverage of primary mother-to-child HIV transmission isolates by second-generation broadly neutralizing antibodies.AIDS (London, England) · 2013Article
- Neutralizing epitopes in the membrane-proximal external region of HIV-1 gp41 are influenced by the transmembrane domain and the plasma membrane.Journal of virology · 2012Article
- Genotypic and functional properties of early infant HIV-1 envelopes.Retrovirology · 2011Article
- Searching for an effective, safe and universal anti-HIV vaccine: Finding the answer in just one short peptide.Self/nonself · 2011Article
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- Article
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 2 countries.
Funding
Abstract
Human antibody 4E10 targets the highly conserved membrane-proximal external region (MPER) of the HIV-1 transmembrane glycoprotein, gp41, and has extraordinarily broad neutralizing activity. It is considered by many to be a prototype for vaccine development. In this study, we describe four subjects infected with viruses carrying rare MPER polymorphisms associated with resistance to 4E10 neutralization. In one case resistant virus carrying a W680G substitution was transmitted from mother to infant. We used site-directed mutagenesis to demonstrate that the W680G substitution is necessary for conferring the 4E10-resistant phenotype, but that it is not sufficient to transfer the phenotype to a 4E10-sensitive Env. Our third subject carried Envs with a W680R substitution causing variable resistance to 4E10, indicating that residues outside the MPER are required to confer the phenotype. A fourth subject possessed a F673L substitution previously associated with 4E10 resistance. For all three subjects with W680 polymorphisms, we observed additional residues in the MPER that co-varied with position 680 and preserved charged distributions across this region. Our data provide important caveats for vaccine development targeting the MPER. Naturally occurring Env variants described in our study also represent unique tools for probing the structure-function of HIV-1 envelope.
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Registered trials
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.