Open AccessGenetic and Functional Analysis of R5X4 Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Derived from Two Individuals Homozygous for the CCR5Δ32 Allele
Author(s) -
Lachlan Robert Gray,
Melissa Churchill,
N.M. Keane,
Jasminka Sterjovski,
Anne Ellett,
Damian F. J. Purcell,
Pantelis Poumbourios,
Chenda Kol,
Bin Wang,
Nitin K. Saksena,
Steven Lodewyk Wesselingh,
Patricia Price,
Martyn A. French,
Dana Gabuzda,
Paul R Gorry
Publication year - 2006
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.80.7.3684-3691.2006
Subject(s) - biology , virology , glycoprotein , peripheral blood mononuclear cell , virus , mutation , allele , transfection , cxcr4 , immunology , viral envelope , viral entry , lymphocyte , monocyte , genetics , gene , chemokine , in vitro , viral replication , immune system
We characterized human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) isolated from two HIV-1-infected CCR5Δ32 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 CCR5Δ32 homozygotes suggests the conserved CCR5 binding domain of Env is highly stable and provides new mechanistic insights important for HIV-1 transmission and persistence.