Enterovirus 71 spreads from peripheral inoculation sites to the central nervous system in mice primarily via retrograde axonal transport, which was significantly reduced by colchicine.
Demonstrates that enterovirus 71 neuroinvasion occurs primarily via retrograde axonal transport rather than hematogenous spread in a mouse model.
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 et al. (Thu,) conducted a other in Enterovirus 71 infection. Enterovirus 71 (EV71/MP4 strain) inoculation vs. Mock infection or PBS was evaluated on Viral transmission route and neuroinvasion. Enterovirus 71 spreads from peripheral inoculation sites to the central nervous system in mice primarily via retrograde axonal transport, which was significantly reduced by colchicine.