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
Macfarlane Burnet Institute for Medical Research and Public Health, GPO Box 2284, Melbourne 3001, Victoria, Australia.
J Virol. 2006 Apr;80(7):3684-91. doi: 10.1128/JVI.80.7.3684-3691.2006.
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.
我们对从两名感染人类免疫缺陷病毒1型(HIV-1)的CCR5Δ32纯合子中分离出的HIV-1包膜糖蛋白(Env)进行了特征分析。来自两名受试者的Env利用CCR5和CXCR4进入转染细胞。大多数R5X4 Env具有淋巴细胞嗜性,仅利用CXCR4进入外周血单核细胞(PBMC),但有一部分具有淋巴细胞和巨噬细胞双嗜性,利用CCR5或CXCR4进入PBMC和单核细胞衍生的巨噬细胞。在两名CCR5Δ32纯合子中持续存在利用CCR5的HIV-1,这表明Env保守的CCR5结合结构域高度稳定,并为HIV-1传播和持续存在提供了重要的新机制见解。