Journal article
Phenotypic and Immunologic Comparison of Clade B Transmitted/Founder and Chronic HIV-1 Envelope Glycoproteins
Journal of virology, Vol.85(17), pp.8514-8527
09/2011
DOI: 10.1128/JVI.00736-11
PMCID: PMC3165820
PMID: 21715507
Abstract
Sexual transmission of human immunodeficiency virus type 1 (HIV-1) across mucosal barriers is responsible for the vast majority of new infections. This relatively inefficient process results in the transmission of a single transmitted/founder (T/F) virus, from a diverse viral swarm in the donor, in approximately 80% of cases. Here we compared the biological activities of 24 clade B T/F envelopes (Envs) with those from 17 chronic controls to determine whether the genetic bottleneck that occurs during transmission is linked to a particular Env phenotype. To maximize the likelihood of an intact mucosal barrier in the recipients and to enhance the sensitivity of detecting phenotypic differences, only T/F Envs from individuals infected with a single T/F variant were selected. Using pseudotyping to assess Env function in single-round infectivity assays, we compared coreceptor tropism, CCR5 utilization efficiencies, primary CD4
+
T cell subset tropism, dendritic cell
trans
-infections, fusion kinetics, and neutralization sensitivities. T/F and chronic Envs were phenotypically equivalent in most assays; however, T/F Envs were modestly more sensitive to CD4 binding site antibodies b12 and VRC01, as well as pooled human HIV Ig. This finding was independently validated with a panel of 14 additional chronic HIV-1 Env controls. Moreover, the enhanced neutralization sensitivity was associated with more efficient binding of b12 and VRC01 to T/F Env trimers. These data suggest that there are subtle but significant structural differences between T/F and chronic clade B Envs that may have implications for HIV-1 transmission and the design of effective vaccines.
Details
- Title: Subtitle
- Phenotypic and Immunologic Comparison of Clade B Transmitted/Founder and Chronic HIV-1 Envelope Glycoproteins
- Creators
- Craig B Wilen - Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104Nicholas F Parrish - Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294Jennifer M Pfaff - Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104Julie M Decker - Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294Elizabeth A Henning - Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104Hillel Haim - Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MassachusettsJosiah E Petersen - Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104Jason A Wojcechowskyj - Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104Joseph Sodroski - Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MassachusettsBarton F Haynes - Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina 27710David C Montefiori - Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina 27710John C Tilton - Department of General Medical Sciences, Center for Proteomics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106George M Shaw - Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294Beatrice H Hahn - Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294Robert W Doms - Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.85(17), pp.8514-8527
- DOI
- 10.1128/JVI.00736-11
- PMID
- 21715507
- PMCID
- PMC3165820
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 09/2011
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083264002771
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