Retrograde axonal transport: a major transmission route of enterovirus 71 in mice.
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.
Chen
Che-Szu
CS
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.
Yao
Yi-Chuan
YC
Lin
Shin-Chao
SC
Lee
Yi-Ping
YP
Wang
Ya-Fang
YF
Wang
Jen-Ren
JR
Liu
Ching-Chuan
CC
Lei
Huan-Yao
HY
Yu
Chun-Keung
CK
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D001369:Axons / Q000821:virology*; D001921:Brain / Q000473:pathology / Q000821:virology; D003078:Colchicine / Q000494:pharmacology; D004195:Disease Models, Animal; D004770:Enterovirus / Q000502:physiology*; D004769:Enterovirus Infections / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D013116:Spinal Cord / Q000821:virology; D016019:Survival Analysis; D014766:Viremia
D003078:Colchicine