Use of type 1/type 2 chimeric polioviruses to study determinants of poliovirus type 1 neurovirulence in a mouse model.
We previously described the characteristics of a type 1/type 2 (PV-1/PV-2) chimeric poliovirus, v510, which contains the six amino acids specific for PV-2 in the B-C loop of VP1. This virus was found to be mouse-adapted, as PV-2 and in contrast with PV-1. Determinants of host range were studied in detail and are reported here. PV-1/PV-2 chimeras containing partial PV-1----PV-2 substitutions in the B-C loop of VP1 were obtained by making use of a mutagenesis cartridge on PV-1 cDNA. Analysis of mouse neurovirulence of these chimeras, when correlated with the three-dimensional structure of the v510 capsid, revealed that PV-2 residues important for mouse tropism are those which determine the particular conformation of the B-C loop of VP1 in v510. The mutation of the adenine residue at position 480 of the 5' noncoding region into a guanine residue has been shown to be an important determinant of PV-1 attenuation in monkeys. We show that introduction of this mutation in the v510 genome results in a virus which is partially attenuated for mice. This suggests that analysis of genomic determinants important for PV-1 neurovirulence could be carried out in a mouse model by making use of a mouse-adapted PV-1/PV-2 chimera.
Martin
A
A
Laboratory of Molecular Virology, CNRS URA 545, Pasteur Institute, Paris, France.
Benichou
D
D
Couderc
T
T
Hogle
J M
JM
Wychowski
C
C
Van der Werf
S
S
Girard
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002213:Capsid / Q000235:genetics*; D036022:Capsid Proteins; D002678:Chimera; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D008526:Medulla Oblongata / Q000382:microbiology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D015345:Oligonucleotide Probes; D010957:Plasmids; D017955:Poliovirus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D011487:Protein Conformation; D013116:Spinal Cord / Q000382:microbiology*; D014774:Virulence
D036022:Capsid Proteins; D015345:Oligonucleotide Probes; C442540:VP1 protein, Poliovirus