High level of coreceptor-independent HIV transfer induced by contacts between primary CD4 T cells

被引:84
作者
Blanco, J
Bosch, B
Fernández-Figueras, MT
Barretina, J
Clotet, B
Esté, JA
机构
[1] Hosp Univ Germans Trias & Pujol, Fdn IrsiCaixa, Lab Retrovirol, Barcelona 08916, Spain
[2] Hosp Univ Germans Trias & Pujol, Dept Pathol, Barcelona 08916, Spain
关键词
D O I
10.1074/jbc.M408547200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cell-to-cell virus transmission is one of the most efficient mechanisms of human immunodeficiency virus (HIV) spread, requires CD4 and coreceptor expression in target cells, and may also lead to syncytium formation and cell death. Here, we show that in addition to this classical coreceptor-mediated transmission, the contact between HIV-producing cells and primary CD4 T cells lacking the appropriate coreceptor induced the uptake of HIV particles by target cells in the absence of membrane fusion or productive HIV replication. HIV uptake by CD4 T cells required cellular contacts mediated by the binding of gp120 to CD4 and intact actin cytoskeleton. HIV antigens taken up by CD4 T cells were rapidly endocytosed to trypsin-resistant compartments inducing a partial disappearance of CD4 molecules from the cell surface. Once the cellular contact was stopped, captured HIV were released as infectious particles. Electron microscopy revealed that HIV particles attached to the surface of target cells and accumulated in large (0.5 - 1.0 mum) intracellular vesicles containing 1 - 14 virions, without any evidence for massive clathrin-mediated HIV endocytosis. The capture of HIV particles into trypsin-resistant compartments required the availability of the gp120 binding site of CD4 but was independent of the intracytoplasmic tail of CD4. In conclusion, we describe a novel mechanism of HIV transmission, activated by the contact of infected and uninfected primary CD4 T cells, by which HIV could exploit CD4 T cells lacking the appropriate coreceptor as an itinerant virus reservoir.
引用
收藏
页码:51305 / 51314
页数:10
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