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Journal of Virology, September 2007, p. 8996-9003, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00236-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Retrograde Axonal Transport: a Major Transmission Route of Enterovirus 71 in Mice{triangledown}

Che-Szu Chen,1,{dagger} Yi-Chuan Yao,1,{dagger} Shin-Chao Lin,1,{dagger} Yi-Ping Lee,2 Ya-Fang Wang,2 Jen-Ren Wang,3 Ching-Chuan Liu,4 Huan-Yao Lei,1 and Chun-Keung Yu1*

Department of Microbiology and Immunology,1 Institute of Basic Medical Sciences,2 Department of Medical Laboratory Science and Biotechnology,3 Department of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China4

Received 4 February 2007/ Accepted 5 June 2007

Inoculation of enterovirus 71 (EV71) by the oral (p.o.), intramuscular (i.m.), or intracranial route resulted in brain infection, flaccid paralysis, pulmonary dysfunction, and death of 7-day-old mice. The lag time of disease progression indicated that neuroinvasion from the inoculation sites was a prerequisite for the development of the clinical signs. Although EV71 p.o. inoculation led to a persistent viremia and a transient increase in blood-brain barrier permeability at the early stage of the infection, only low levels of virus, which led to neither severe infection nor clinical illness, could be detected in the brain, suggesting that hematogenous transport might not represent a major transmission route. In the spinal cord, following both p.o. and hind limb i.m. inoculation, the virus first appeared and increased rapidly in the lower segments, especially at the anterior horn areas, and then spread to the upper segments and brain in the presence of viremia. A reverse pattern, with the virus being first detected in the upper segment, was observed when the virus was i.m. inoculated in the forelimb. Colchicine, a fast axonal transport inhibitor, but not sciatic nerve transection reduced EV71 neuroinvasion in a dose-dependent manner, indicating a neuronal transmission of the virus.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China. Phone: 886-6-2353535, ext. 5673. Fax: 886-6-2082705. E-mail address: dckyu{at}mail.ncku.edu.tw

{triangledown} Published ahead of print on 13 June 2007.

{dagger} C.-S. Chen, Y.-C. Yao, and S.-C. Lin contributed equally to this study.

Journal of Virology, September 2007, p. 8996-9003, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00236-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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