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Basic Characteristics of Mutations
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Mutation Site
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V293E |
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Mutation Site Sentence
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To explore protein-protein interactions at the SF12-Env interface, we examined mutations in positions 214gp120 (P214I, P214Q), 291gp120 (S291P, S291T), 293gp120 (Q/V293E, Q/V293K, Q/V293R), and 444gp120 (R444T) in the Envs of the BG505 and YU2 pseudoviruses. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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gp120 |
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Standardized Encoding Gene
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Env
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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"HIV-1YU2, HIV-1BG505"
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Functional Impact and Mechanisms
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Disease
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HIV Infections
|
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Immune
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- |
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Target Gene
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-
|
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Clinical and Epidemiological Correlations
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Clinical Information
|
Y |
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Treatment
|
- |
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Location
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USA |
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Literature Information
|
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PMID
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31126879
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Title
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Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope
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Author
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Schoofs T,Barnes CO,Suh-Toma N,Golijanin J,Schommers P,Gruell H,West AP Jr,Bach F,Lee YE,Nogueira L,Georgiev IS,Bailer RT,Czartoski J,Mascola JR,Seaman MS,McElrath MJ,Doria-Rose NA,Klein F,Nussenzweig MC,Bjorkman PJ
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Journal
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Immunity
|
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Journal Info
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2019 Jun 18;50(6):1513-1529
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Abstract
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Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env's silent face and was potent against clade AE viruses, which are poorly covered by V3-glycan bNAbs. A 3.3A cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silentface antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448(gp120) glycan. Effective bNAbs can therefore be raised against HIV-1 Env's silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development.
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Sequence Data
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MK722158-MK722171
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