Deleting two amino acids in glycoprotein gI of pseudorabies virus decreases virulence and neurotropism for pigs, but does not affect immunogenicity.

The virulence, pathogenicity and immunogenicity of two pseudorabies virus (PRV) variants were investigated in 3-week-old pigs that had been intranasally infected. Variant M303 (delta 125,126) lacked amino acids valine (125) and cysteine(126) in an immunodominant antigenic region of glycoprotein I (gI) containing two discontinuous antigenic domains, whereas M304 (delta 59,60) lacked amino acids glycine(59) and aspartic acid(60) in a continuous antigenic domain. M303 (delta 125,126) was not virulent for pigs, but M304 (delta 59,60) was as virulent as wild-type PRV: all pigs died within 8 days of infection. Both gI mutant viruses replicated in the oropharyngeal mucosa, although M304 (delta 59,60) replicated to higher virus titres than M303 (delta 125,126), and virus was recovered from various tissues. However, in contrast to M304 (delta 59,60), M303 (delta 125,126) was not recovered from any central nervous system (CNS) tissues examined. Thus, the tendency of PRV to locate in the CNS was markedly reduced by deleting amino acids valine(125) and cysteine(126) of gI. Pigs immunized with M303 were completely protected against challenge infection; no clinical signs of disease were detected, no virus was shed, and no secondary antibody response was detected. Thus, deleting amino acids valine(125) and cysteine(126) in gI decreases virulence and neurotropism and does not affect immunogenicity.