期刊
VIROLOGY
卷 413, 期 1, 页码 12-18出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2011.02.014
关键词
HSV entry; Bispecific adapter; EGF receptor; Endocytosis; Fusion
类别
资金
- NIH [NS040923, CA119298]
- Japanese Ministry of Education, Culture, Science, Sports and Technology [21390374]
- Grants-in-Aid for Scientific Research [21249069, 21390374, 23686118, 22226013] Funding Source: KAKEN
Herpes simplex virus entry into cells requires the binding of envelope glycoprotein D (gD) to an entry receptor. Depending on the cell, entry occurs by different mechanisms, including fusion at the cell surface or endocytosis. Here we examined the entry mechanism through a non-HSV receptor mediated by a soluble bispecific adapter protein composed of recognition elements for gD and the EGF receptor (EGFR). Virus entered into endosomes using either EGF or an EGFR-specific single chain antibody (scFv) for receptor recognition. Infection was less efficient with the EGF adapter which could be attributed to its weaker binding to a viral gD. Infection mediated by the scFy adapter was pH sensitive, indicating that gD-EGFR bridging alone was insufficient for capsid release from endosomes. We also show that the scFv adapter enhanced infection of EGFR-expressing tumor tissue in vivo. Our results indicate that adapters may retarget HSV infection without drastically changing the entry mechanism. (C) 2011 Elsevier Inc. All rights reserved.
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