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Journal of Virology, July 2004, p. 7186-7198, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.7186-7198.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Receptor (CD155)-Dependent Endocytosis of Poliovirus and Retrograde Axonal Transport of the Endosome

Seii Ohka,1 Norie Matsuda,1 Koujiro Tohyama,2 Toshiyuki Oda,1 Masato Morikawa,1 Shusuke Kuge,1 and Akio Nomoto1*

Department of Microbiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033,1 The Center for Electron Microscopy and Bio-Imaging Research, Department of Neuroanatomy, Iwate Medical University, Morioka, Iwate 020-8505, Japan2

Received 19 November 2003/ Accepted 18 February 2004

Poliovirus (PV), when injected intramuscularly into the calf, is incorporated into the sciatic nerve and causes an initial paralysis of the inoculated limb in transgenic mice carrying the human PV receptor (hPVR/CD155) gene. Here, we demonstrated by using an immunoelectron microscope that PV particles exist on vesicle structures in nerve terminals of neuromuscular junctions. We also demonstrated in glutathione S-transferase pull-down experiments that the dynein light chain, Tctex-1, interacts directly with the cytoplasmic domain of hPVR. In the axons of differentiated rat PC12 cells transfected with expression vectors for hPVRs, vesicles composed of PV and hPVR{alpha}, as well as a mutant hPVR{alpha} (hPVRM{alpha}) that had a reduced ability to bind Tctex-1, colocalized with Tctex-1. However, vesicles containing PV, dextran, and hPVR{alpha} had only retrograde motion, while those containing PV, dextran, and hPVRM{alpha} had anterograde or retrograde motion. Topical application of the antimicrotubule agent vinblastine to the sciatic nerve reduced the amount of virus transported from the calf to the spinal cord. These results suggest that direct efficient interaction between the cytoplasmic domain and Tctex-1 is essential for the efficient retrograde transport of PV-containing vesicles along microtubules in vivo.


* Corresponding author. Mailing address: Department of Microbiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Phone: 81-3-5841-3407. Fax: 81-3-5841-3374. E-mail: anomoto{at}m.u-tokyo.ac.jp.


Journal of Virology, July 2004, p. 7186-7198, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.7186-7198.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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