West Nile virus-induced acute flaccid paralysis is prevented by monoclonal antibody treatment when administered after infection of spinal cord neurons.
Acute flaccid polio-like paralysis occurs during natural West Nile virus (WNV) infection in a subset of cases in animals and humans. To evaluate the pathology and the possibility for therapeutic intervention, the authors developed a model of acute flaccid paralysis by injecting WNV directly into the sciatic nerve or spinal cord of hamsters. By directly injecting selected sites of the nervous system with WNV, the authors mapped the lesions responsible for hind limb paralysis to the lumbar spinal cord. Immunohistochemical analysis of spinal cord sections from paralyzed hamsters revealed that WNV-infected neurons localized primarily to the ventral motor horn of the gray matter, consistent with the polio-like clinical presentation. Neuronal apoptosis and diminished cell function were identified by TUNEL (terminal deoxynucleotidyl transferase-mediated BrdUTP nick end labeling) and choline acetyltransferase staining, respectively. Administration of hE16, a potently neutralizing humanized anti-WNV monoclonal antibody, 2 to 3 days after direct WNV infection of the spinal cord, significantly reduced paralysis and mortality. Additionally, a single injection of hE16 as late as 5 days after WNV inoculation of the sciatic nerve also prevented paralysis. Overall, these experiments establish that WNV-induced acute flaccid paralysis in hamsters is due to neuronal infection and injury in the lumbar spinal cord and that treatment with a therapeutic antibody prevents paralysis when administered after WNV infection of spinal cord neurons.
Morrey
John D
JD
Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah 84322-4700, USA. john.morrey@usu.edu
Siddharthan
Venkatraman
V
Wang
Hong
H
Hall
Jeffery O
JO
Skirpstunas
Ramona T
RT
Olsen
Aaron L
AL
Nordstrom
Jeffrey L
JL
Koenig
Scott
S
Johnson
Syd
S
Diamond
Michael S
MS
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000627:therapeutic use; D006224:Cricetinae; D009474:Neurons / Q000473:pathology; D010243:Paralysis / Q000517:prevention & control* / Q000821:virology; D013116:Spinal Cord / Q000473:pathology / Q000821:virology; D053586:Virus Internalization; D014901:West Nile Fever / Q000150:complications*; D014902:West Nile virus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents