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The HIV-1 envelope (Env) spike is a trimer of gp120/gp41 heterodimers that mediates viral entry. Binding to CD4 on the host cell membrane is the first essential step for infection but disrupts the native antigenic state of Env, posing a key obstacle to vaccine development. We locked the HIV-1 Env trimer in a pre-fusion configuration, resulting in impaired CD4 binding and enhanced binding to broadly neutralizing antibodies. This design was achieved via structure-guided introduction of neo-disulfide bonds bridging the gp120 inner and outer domains and was successfully applied to soluble trimers and native gp160 from different HIV-1 clades. Crystallization illustrated the structural basis for CD4-binding impairment. Immunization of rabbits with locked trimers from two different clades elicited neutralizing antibodies against tier-2 viruses with a repaired glycan shield regardless of treatment with a functional CD4 mimic. Thus, interdomain stabilization provides a widely applicable template for the design of Env-based HIV-1 vaccines.
Pubmed ID: 29902444 RIS Download
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Web application to generate sequence logos, graphical representations of patterns within multiple sequence alignment. Designed to make generation of sequence logos easy. Sequence logo generator.
View all literature mentionsSemi-automatic crystallographic data collection software that integrates data collection, data reduction, phasing and model building in a single software package.
View all literature mentionsNIH HIV Reagent Program has been managed under contract by American Type Culture Collection (ATCC) since 2020. ATCC shall maintain the NIH HIV Reagent Program through identification, acquisition, production, receipt, storage, maintenance, distribution and disposal of biological and chemical research organisms and materials for HIV and other infectious diseases for use in basic and translational research.
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View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
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