TY - JOUR
T1 - Mechanism of HSV infection through soluble adapter-mediated virus bridging to the EGF receptor
AU - Nakano, Kenji
AU - Kobayashi, Masatoshi
AU - Nakamura, Kei Ichiro
AU - Nakanishi, Takeshi
AU - Asano, Ryutaro
AU - Kumagai, Izumi
AU - Tahara, Hideaki
AU - Kuwano, Michihiko
AU - Cohen, Justus B.
AU - Glorioso, Joseph C.
N1 - Funding Information:
We thank Dr. Yasushi Kawaguchi and Ms. Setsuko Nakayama (Tokyo) for the technical assistance and Drs. William Goins and Hiroaki Uchida (Pittsburgh) for the helpful discussions. This work was supported by NIH grants NS040923 and CA119298 to J.C.G. and by a grant from the Japanese Ministry of Education, Culture, Science, Sports and Technology to K.N. (grants-in-aid for scientific research # 21390374 ).
PY - 2011/4/25
Y1 - 2011/4/25
N2 - 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 bi-specific 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 scFv 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.
AB - 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 bi-specific 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 scFv 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.
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U2 - 10.1016/j.virol.2011.02.014
DO - 10.1016/j.virol.2011.02.014
M3 - Article
C2 - 21382632
AN - SCOPUS:79953072979
SN - 0042-6822
VL - 413
SP - 12
EP - 18
JO - Virology
JF - Virology
IS - 1
ER -