Quantitative analysis of poliomyelitis-like paralysis in mice induced by a poliovirus replicon.
Poliovirus (PV) infection causes severe paralysis, typically of the legs, by destruction of the motor neurons in the spinal cord. In this study, the relationship between PV replication in the spinal cord, damage in the motor neurons and poliomyelitis-like paralysis was analysed in transgenic mice expressing the human PV receptor (TgPVR21). First, a PV replicon encoding firefly luciferase in place of the capsid genes (PV-Fluc mc) was trans-encapsidated in 293T cells and the trans-encapsidated PV-Fluc mc (TE-PV-Fluc mc) was then inoculated into the spinal cords of TgPVR21 mice. TE-PV-Fluc mc was recovered with a titre of 6.3 x 10(7) infectious units ml(-1), which was comparable to those of PV1 strains. TgPVR21 mice inoculated with TE-PV-Fluc mc showed non-lethal paralysis of the hindlimbs, with severity ranging from a decline in grip strength to complete flaccid paralysis. The replication of TE-PV-Fluc mc in the spinal cord reached peak levels at 10 h post-inoculation (p.i.), followed by the appearance of paralysis at as early as 12 h p.i., reaching a plateau at 16 h p.i. Histological analysis showed a correlation between the lesion and the severity of the clinical symptoms in most mice. However, severe paralysis could also be observed with an apparently low lesion score, where as few as 5.3 x 10(2) motor neurons (1.4 % of the susceptible cells in the lumbar cord) were infected by TE-PV-Fluc mc. These results indicate that PV replication in a small population of the motor neurons was critical for severe residual poliomyelitis-like paralysis in TgPVR21 mice.
Arita
Minetaro
M
Department of Virology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
Nagata
Noriyo
N
Department of Pathology, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
Sata
Tetsutaro
T
Department of Pathology, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
Miyamura
Tatsuo
T
Department of Virology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
Shimizu
Hiroyuki
H
Department of Virology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
D000818:Animals; D002213:Capsid / Q000378:metabolism; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D049409:Luciferases, Firefly / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology; D010243:Paralysis / Q000473:pathology*; D011051:Poliomyelitis / Q000473:pathology* / Q000821:virology*; D017955:Poliovirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D011991:Receptors, Virus / Q000378:metabolism; D012093:Replicon / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D014779:Virus Replication
D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor; D049409:Luciferases, Firefly