Genetic and functional analysis of R5X4 human immunodeficiency virus type 1 envelope glycoproteins derived from two individuals homozygous for the CCR5delta32 allele |
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Authors: | Gray Lachlan Churchill Melissa J Keane Niamh Sterjovski Jasminka Ellett Anne M Purcell Damian F J Poumbourios Pantelis Kol Chenda Wang Bin Saksena Nitin K Wesselingh Steven L Price Patricia French Martyn Gabuzda Dana Gorry Paul R |
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Affiliation: | Macfarlane Burnet Institute for Medical Research and Public Health, GPO Box 2284, Melbourne 3001, Victoria, Australia. |
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Abstract: | We characterized human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) isolated from two HIV-1-infected CCR5delta32 homozygotes. Envs from both subjects used CCR5 and CXCR4 for entry into transfected cells. Most R5X4 Envs were lymphocyte-tropic and used CXCR4 exclusively for entry into peripheral blood mononuclear cells (PBMC), but a subset was dually lymphocyte- and macrophage-tropic and used either CCR5 or CXCR4 for entry into PBMC and monocyte-derived macrophages. The persistence of CCR5-using HIV-1 in two CCR5delta32 homozygotes suggests the conserved CCR5 binding domain of Env is highly stable and provides new mechanistic insights important for HIV-1 transmission and persistence. |
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