Regulation of adenovirus membrane penetration by the cytoplasmic tail of integrin β5

被引:56
作者
Wang, K
Guan, TL
Cheresh, DA
Nemerow, GR
机构
[1] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
关键词
D O I
10.1128/JVI.74.6.2731-2739.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Adenovirus (Ad) cell entry involves sequential interactions with host cell receptors that mediate attachment (CAR), internalization (alpha v beta 3 and alpha v beta 5), and penetration (alpha v beta 5) of the endosomal membrane. These events allow the virus to deliver its genome to the nucleus. While integrins alpha v beta 3 and alpha v beta 5 both promote Ad internalization into cells, integrin alpha v beta 5 selectively facilitates Ad-mediated membrane permeabilization and endosome rupture. In the experiments reported herein, we demonstrate that the intracellular domain of the integrin beta 5 subunit specifically regulates Ad-mediated membrane permeabilization and gene delivery. CS-1 melanoma cells expressing a truncated integrin beta 5 or a chimeric (beta 5-beta 3) cytoplasmic tail (CT) supported normal levels of Ad endocytosis but had reduced Ad-mediated gene delivery and membrane permeabilization relative to cells expressing a wild-type integrin beta 5, Thin-section electron microscopy revealed that virion particles were capable of being endocytosed into cells expressing a truncated beta 5CT, but they failed to escape cytoplasmic vesicles and translocate to the nucleus. Site-specific mutagenesis studies suggest that a C-terminal TVD motif in the beta 5CT plays a major role in Ad membrane penetration.
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收藏
页码:2731 / 2739
页数:9
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