期刊
NATURE MEDICINE
卷 17, 期 1, 页码 96-U273出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2270
关键词
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资金
- US National Institutes of Health [R01 CA080192, R01 HLA078836]
- Pacific Ovarian Cancer Research Consortium/Specialized Program of Research Excellence in Ovarian Cancer [P50 CA83636]
- NATIONAL CANCER INSTITUTE [R01CA136487, P50CA083636, R01CA144057, R01CA080192] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR025014] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI072774] Funding Source: NIH RePORTER
We have identified desmoglein-2 (DSG-2) as the primary high-affinity receptor used by adenoviruses Ad3, Ad7, Ad11 and Ad14. These serotypes represent key human pathogens causing respiratory and urinary tract infections. In epithelial cells, adenovirus binding of DSG-2 triggers events reminiscent of epithelial-to-mesenchymal transition, leading to transient opening of intercellular junctions. This opening improves access to receptors, for example, CD46 and Her2/neu, that are trapped in intercellular junctions. In addition to complete virions, dodecahedral particles (PtDds), formed by excess amounts of viral capsid proteins, penton base and fiber during viral replication, can trigger DSG-2-mediated opening of intercellular junctions as shown by studies with recombinant Ad3 PtDds. Our findings shed light on adenovirus biology and pathogenesis and may have implications for cancer therapy.
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