Poliovirus Host Range Is Determined by a Short Amino Acid Sequence in Neutralization Antigenic Site I

• DOI: 10.1126/science.2838906
• Publication Date: 2006-10-05T21:21:15Z
• Authors: Michael G. Murray; Jonathan Bradley; Xiao-Feng Yang; Eckard Wimmer; Eric G. Moss; Vincent R. Racani...
• Keywords: 0301 basic medicine; 0303 health sciences; DNA Mutational Analysis; Antibodies, Viral; Virus Replication; 3. Good health; Mice; Poliovirus; 03 medical and health sciences; Capsid; Neutralization Tests; Animals; Nervous System Diseases; Antigens, Viral

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.