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Conserved determinants of enhanced CCR5 binding in the human immunodeficiency virus subtype D envelope third variable loop
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Metadata
Document Title
Conserved determinants of enhanced CCR5 binding in the human immunodeficiency virus subtype D envelope third variable loop
Author
Teeravechyan S., Essex M., Lee T.-H.
Name from Authors Collection
Affiliations
Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, United States; National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 113 Thailand Science Park, Klong Luang, Pathumthani 12120, Thailand
Type
Article
Source Title
AIDS Research and Human Retroviruses
ISSN
08892229
Year
2010
Volume
26
Issue
4
Page
481-488
Open Access
Green
DOI
10.1089/aid.2009.0086
Abstract
Human immunodeficiency virus 1 subtype D (HIV-1D) contributes to a significant portion of the HIV-1 disease burden in eastern and central Africa, and is associated with more rapid disease progression. Its viral envelope sequences, particularly in the third variable region (V3), are highly divergent from other major subtypes yet have rarely been studied to date. We evaluated the V3 and select bridging sheet residues of the HIV-1D 94UG114 envelope by alanine-scanning mutagenesis to determine the residues involved in CCR5 usage conservation in the face of sequence variability. We found most single alanine mutations capable of abolishing CCR5 binding, suggesting binding contacts that are highly sensitive to mutation. Despite drastic binding defects across the board, most mutants mediated fusion at or near wild-type levels, demonstrating an ability to accommodate changes in CCR5 affinity while maintaining the ability to complete entry. Three of the alanine mutations did not abolish CCR5 binding but rather resulted in enhanced CCR5 binding. The positions of these residues were found to be conserved between strains of two subtypes, revealing similar V3 elements that suggest a conservation of constraints in V3 loop conformation. © Copyright 2010 Mary Ann Liebert, Inc.
Funding Sponsor
Fogarty International Center
License
CC BY
Rights
Author
Publication Source
Scopus