Experimental reovirus-induced acute flaccid paralysis and spinal motor neuron cell death.
Acute flaccid paralysis (AFP) describes the loss of motor function in 1 or more limbs commonly associated with viral infection and destruction of motor neurons in the anterior horns of the spinal cord. Therapy is limited, and the development of effective treatments is hampered by a lack of experimental models. Reovirus infection of neonatal mice provides a model for the study of CNS viral infection pathogenesis. Injection of the Reovirus serot Type 3 strains Abney (T3A) or Dearing (T3D) into the hindlimb of 1-day-old mice resulted in the development of AFP in more than 90% of infected mice. Acute flaccid paralysis began in the ipsilateral hindlimb at 8 to 10 days postinfection and progressed to paraplegia 24 hours later. Paralysis correlated with injury, neuron loss, and spread of viral antigen first to the ipsilateral and then to the contralateral anterior horns. As demonstrated by the activation of caspase 3 and its colocalization with viral antigen in the anterior horn and concomitant cleavage of poly-(adenosine diphosphate-ribose) polymerase, AFP was associated with apoptosis. Calpain activity and inducible nitric oxide synthase expression were both elevated in the spinal cords of paralyzed animals. This study represents the first detailed characterization of a novel and highly efficient experimental model of virus-induced AFP that will facilitate evaluation of therapeutic strategies targeting virus-induced paralysis.
Goody
Robin J
RJ
Department of Neurology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Schittone
Stephanie A
SA
Tyler
Kenneth L
KL
D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral / Q000032:analysis / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002154:Calpain / Q000032:analysis / Q000378:metabolism; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D012089:Mammalian orthoreovirus 3 / Q000472:pathogenicity / Q000502:physiology; D051379:Mice; D016472:Motor Neuron Disease / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D009046:Motor Neurons / Q000473:pathology / Q000821:virology*; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000378:metabolism; D010243:Paralysis / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000378:metabolism; D012088:Reoviridae Infections / Q000473:pathology* / Q000503:physiopathology; D013118:Spinal Cord Diseases / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D014901:West Nile Fever / Q000473:pathology / Q000503:physiopathology
D000956:Antigens, Viral; D015415:Biomarkers; D052247:Nitric Oxide Synthase Type II; D011065:Poly(ADP-ribose) Polymerases; D002154:Calpain; D053148:Caspase 3