Engineering a poliovirus type 2 antigenic site on a type 1 capsid results in a chimaeric virus which is neurovirulent for mice.
Poliovirus type 2 (PV-2) Lansing strain produces a fatal paralytic disease in mice after intracerebral injection, whereas poliovirus type 1 (PV-1) Mahoney strain causes disease only in primates. Atomic models derived from the three-dimensional crystal structure of the PV-1 Mahoney strain have been used to locate three antigenic sites on the surface of the virion. We report here the construction of type 1-type 2 chimaeric polioviruses in which antigenic site 1 from the PV-1 Mahoney strain was substituted by that of the PV-2 Lansing strain by nucleotide cassette exchange in a cloned PV-1 cDNA molecule. These chimaeras proved to have mosaic capsids with composite type 1 and type 2 antigenicity, and induced a neutralizing response against both PV-1 and PV-2 when injected into rabbits. Moreover, a six-amino-acid change in PV-1 antigenic site 1 was shown to be responsible for a remarkable host-range mutation in so far as one of the two type 1-type 2 chimaera was highly neurovirulent for mice.
Martin
A
A
Laboratory of Molecular Virology, CNRS UA 545, Paris, France.
Wychowski
C
C
Couderc
T
T
Crainic
R
R
Hogle
J
J
Girard
M
M
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000235:genetics*; D001483:Base Sequence; D002213:Capsid / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002678:Chimera; D003460:Crystallization; D004262:DNA Restriction Enzymes; D004279:DNA, Viral / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010957:Plasmids; D017955:Poliovirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D011817:Rabbits; D013116:Spinal Cord / Q000382:microbiology; D014771:Virion / Q000235:genetics / Q000276:immunology; D014774:Virulence
D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral; D000939:Epitopes; D004262:DNA Restriction Enzymes