Genotypic and functional properties of early infant HIV-1 envelopes
AuthorsKishko, Michael G.
Brewster, Frank E.
Sullivan, John L.
Clapham, Paul R.
UMass Chan AffiliationsGraduate School of Biomedical Sciences, Immunology and Virology Program
Program in Molecular Medicine
Department of Pediatrics
Infant, Newborn, Diseases
Infectious Disease Transmission, Vertical
env Gene Products, Human Immunodeficiency Virus
Immunology and Infectious Disease
Medicine and Health Sciences
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AbstractBACKGROUND: 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 (IC >/= 100 mug/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.
SourceRetrovirology. 2011 Aug 15;8:67. Link to article on publisher's site 2011 Kishko et al; licensee BioMed Central Ltd.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/39468
PubMed ID21843318; 21843318
Related ResourcesLink to Article in PubMed
Rights© 2011 Kishko et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.