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.
机构:
UNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USAUNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USA
Chang, DD
;
Wong, C
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UNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USAUNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USA
Wong, C
;
Smith, H
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UNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USAUNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USA
Smith, H
;
Liu, J
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UNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USAUNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USA
机构:
UNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USAUNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USA
Chang, DD
;
Wong, C
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h-index: 0
机构:
UNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USAUNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USA
Wong, C
;
Smith, H
论文数: 0引用数: 0
h-index: 0
机构:
UNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USAUNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USA
Smith, H
;
Liu, J
论文数: 0引用数: 0
h-index: 0
机构:
UNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USAUNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90095 USA