Genotypic and functional properties of early infant HIV-1 envelopes.
Retrovirology
; 8: 67, 2011 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-21843318
ABSTRACT
BACKGROUND:
Understanding the properties of HIV-1 variants that are transmitted from women to their infants is crucial to improving strategies to prevent transmission. In this study, 162 full-length envelope (env) clones were generated from plasma RNA obtained from 5 HIV-1 Clade B infected mother-infant pairs. Following extensive genotypic and phylogenetic analyses, 35 representative clones were selected for functional studies.RESULTS:
Infant quasispecies were highly homogeneous and generally represented minor maternal variants, consistent with transmission across a selective bottleneck. Infant clones did not differ from the maternal in env length, or glycosylation. All infant variants utilized the CCR5 co-receptor, but were not macrophage tropic. Relatively high levels (IC50 ≥ 100 µg/ml) of autologous maternal plasma IgG were required to neutralize maternal and infant viruses; however, all infant viruses were neutralized by pooled sera from HIV-1 infected individuals, implying that they were not inherently neutralization-resistant. All infant viruses were sensitive to the HIV-1 entry inhibitors Enfuvirtide and soluble CD4; none were resistant to Maraviroc. Sensitivity to human monoclonal antibodies 4E10, 2F5, b12 and 2G12 varied.CONCLUSIONS:
This study provides extensive characterization of the genotypic and functional properties of HIV-1 env shortly after transmission. We present the first detailed comparisons of the macrophage tropism of infant and maternal env variants and their sensitivity to Maraviroc, the only CCR5 antagonist approved for therapeutic use. These findings may have implications for improving approaches to prevent mother-to-child HIV-1 transmission.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
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VIH-1
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Transmisión Vertical de Enfermedad Infecciosa
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Productos del Gen env del Virus de la Inmunodeficiencia Humana
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Enfermedades del Recién Nacido
Límite:
Adult
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Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
Retrovirology
Asunto de la revista:
VIROLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos