Engineering a poliovirus type 2 antigenic site on a type 1 capsid results in a chimaeric virus which is neurovirulent for mice.

Abstract

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.