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Basic Characteristics of Mutations
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Mutation Site
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D322A |
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Mutation Site Sentence
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The binding activity of V3-specific IgG MAb H650129 obtained from transmitting woman 3902 was ablated by N-terminal K305Q I307T H308T and K305A I307A mutations and C-terminal F317A A319K D322A, F317L A319T D322R, F317A, and A319K mutations, suggesting that H650129 requires both N- and C-terminal amino acid residues for binding . |
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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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Env |
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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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-
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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
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Y |
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Treatment
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- |
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Location
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US;Malawian |
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Literature Information
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PMID
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32156815
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Title
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Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants
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Author
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Martinez DR,Tu JJ,Kumar A,Mangold JF,Mangan RJ,Goswami R,Giorgi EE,Chen J,Mengual M,Douglas AO,Heimsath H,Saunders KO,Nicely NI,Eudailey J,Hernandez G,Morgan-Asiedu PK,Wiehe K,Haynes BF,Moody MA,LaBranche C,Montefiori DC,Gao F,Permar SR
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Journal
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mBio
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Journal Info
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2020 Mar 10;11(2):e00176-20
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Abstract
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Each year, >180,000 infants become infected via mother-to-child transmission (MTCT) of HIV despite the availability of effective maternal antiretroviral treatments, underlining the need for a maternal HIV vaccine. We characterized 224 maternal HIV envelope (Env)-specific IgG monoclonal antibodies (MAbs) from seven nontransmitting and transmitting HIV-infected U.S. and Malawian mothers and examined their neutralization activities against nontransmitted autologous circulating viruses and infant-transmitted founder (infant-T/F) viruses. Only a small subset of maternal viruses, 3 of 72 (4%), were weakly neutralized by maternal linear V3 epitope-specific IgG MAbs, whereas 6 out of 6 (100%) infant-T/F viruses were neutralization resistant to these V3-specific IgG MAbs. We also show that maternal-plasma broadly neutralizing antibody (bNAb) responses targeting the V3 glycan supersite in a transmitting woman may have selected for an N332 V3 glycan neutralization-resistant infant-T/F virus. These data have important implications for bNAb-eliciting vaccines and passively administered bNAbs in the setting of MTCT.IMPORTANCE Efforts to eliminate MTCT of HIV with antiretroviral therapy (ART) have met little success, with >180,000 infant infections each year worldwide. It is therefore likely that additional immunologic strategies that can synergize with ART will be required to eliminate MTCT of HIV. To this end, understanding the role of maternal HIV Env-specific IgG antibodies in the setting of MTCT is crucial. In this study, we found that maternal-plasma broadly neutralizing antibody (bNAb) responses can select for T/F viruses that initiate infection in infants. We propose that clinical trials testing the efficacy of single bNAb specificities should not include HIV-infected pregnant women, as a single bNAb might select for neutralization-resistant infant-T/F viruses.
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Sequence Data
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-
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