Isolation and molecular characterization of a poliovirus type 1 mutant that replicates in the spinal cords of mice.
The Mahoney strain of poliovirus type 1 (OM) is generally unable to cause paralysis in mice. We isolated a mouse-adapted mutant, PV1/OM-SA (SA), from the spinal cord of a mouse that had been intracerebrally inoculated with OM. SA showed mouse neurovirulence only with intraspinal inoculation, and the infected mice developed a flaccid paralysis, which was indistinguishable from that observed in poliovirus-sensitive transgenic mice inoculated with OM. SA antigens were detected in neurons of the spinal cords of the infected mice. Nucleotide (nt) sequence analysis revealed 9 nt changes on the SA genome, resulting in three amino acid (a.a.) substitutions, i.e., one each in the capsid proteins VP4 and VP1 and in the noncapsid protein 2C. To identify the key mutation site(s) for the mouse neurovirulence, virus recombinants between OM and SA were constructed by using infectious cDNA clones of these two viruses and tested for their mouse neurovirulence after inoculation via an intraspinal route. The results indicated that a mutation at nt 928 (replacement of A with G), resulting in a substitution of Met for Ile at a.a. 62 within VP4, was responsible for conferring the mouse neurovirulence phenotype of the mutant SA. The mutation in VP4 may render the virus accessible to a molecule that acts as a virus receptor and is located on the surfaces of neurons of the mouse spinal cord. This molecule appears not to be expressed in the mouse brain.
Jia
Q
Q
Department of Microbiology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Ohka
S
S
Iwasaki
K
K
Tohyama
K
K
Nomoto
A
A
D000222:Adaptation, Physiological; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002522:Chlorocebus aethiops; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D017955:Poliovirus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D013116:Spinal Cord / Q000276:immunology / Q000821:virology*; D014779:Virus Replication
D005904:Glial Fibrillary Acidic Protein