Poliovirus host range is determined by a short amino acid sequence in neutralization antigenic site I

Abstract

The mouse-adapted strain of poliovirus type 2 (Lansing) induces fatal poliomyelitis in mice after intracerebral inoculation, whereas mice inoculated with poliovirus type 1 (Mahoney) show no signs of disease. Previous work indicated that the adaptation to mouse virulence is associated with the viral capsid proteins and that mutations in neutralization antigenic site I of poliovirus reduce neurovirulence of the Lansing strain in mice. The role of antigenic site I in mouse neurovirulence was further explored by constructing an antigenic hybrid virus. Six amino acids in antigenic site I of the Mahoney strain were replaced with a sequence specific for the Lansing strain by using a mutagenesis cartridge. The hybrid virus was neutralized by polyclonal antisera elicited by the type 1 and type 2 strains of poliovirus and by neutralizing monoclonal antibodies directed against antigenic site I of type 2 virus. The hybrid virus induced paralytic disease in mice, an observation demonstrating that a short sequence of amino acids in antigenic site I is an important determinant of poliovirus host range. Antigenic site I may be involved in attachment of poliovirus to cells of the mouse central nervous system.

Fig. 1

Schematic representation of the poliovirus hybrid showing β sheet B and β sheet C flanking the N-AgI loop (10, 11). Amino acids of PV-1 (M) are shown in the top shaded box and those of W1/2–1D-1 are shown in the bottom box, with the substituted amino acids unshaded. Amino acids identical between PV-1(M) and W1/2– 1D represented by dashes. The mutagenesis cartridge is enclosed in the large box. (●) The naturally occurring Sph I restriction site; (■) the newly generated Hind III restriction site (17). Abbreviations for the amino acid residues are: A, Ala; C, Cys; D, Asp; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; R, Arg; S, Ser; T, Thr; and V, Val.