An anti-phosphoinositide-specific monoclonal antibody that neutralizes HIV-1 infection of human monocyte-derived macrophages

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• 作者：Ousman Jobe^a ; ^b ; Kristina K. Peachman^a ; ^b ; Gary R. Matyas^a ; Ludmila V. Asher^a ; ^b ; Carl R. Alving^a ; Mangala Rao^a ; ^{mrao@hivresearch.org}
• 关键词：Ab ; Antibody ; GalCer ; Galactosyl ceramide ; HIV-1 ; Human immunodeficiency virus type 1 ; M-CSF ; Macrophage colony stimulating factor ; MPER ; Membrane proximal external region ; mAb ; Monoclonal antibody ; MDM ; Monocyte-derived macrophages ; PBMCs ; Peripheral blo
• 刊名：Virology
• 出版年：2012
• 期刊代码：108_00426822
• 类别：imm
• 出版时间：1 September, 2012
• 卷：430
• 期：2
• 页码：110-119
• 文件大小：1190 K

摘要

HIV-1 entry into cells requires the interaction of both HIV-1 envelope proteins and membrane lipids. We investigated the mechanism of neutralization of HIV-1 infection of primary monocyte-derived macrophages (MDM) by a murine monoclonal antibody (mAb) WR321. WR321 specifically binds phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate. These phosphoinositides are present not only on the inner surface of the plasma membranes of cells but also on the surface of virions. HIV-1 acquires these lipids during the budding process. Pre-incubation of WR321 with the virus but not with MDM neutralized HIV-1 infection of MDM. Our results demonstrate that WR321 was internalized only when it was bound to HIV-1. WR321 did not prevent the entry of HIV-1 into MDM. However, once WR321 was internalized along with HIV-1 the mAb acted intracellulary to prevent the release of virions from MDM and also triggered the release of 尾-chemokines.