Emergence of porcine reproductive and respiratory syndrome virus deletion mutants: Correlation with the porcine antibody response to a hypervariable site in the ORF 3 structural glycoprotein

By using porcine immune sera to select a library of phage-displayed random peptides. we identified an antigenic sequence (RKASLSTS) in the C-terminus of the ORF 3 structural glycoprotein of European-type porcine reproductive and respiratory syndrome virus (PRRSV). Through the use of overlapping read ing frames, the same PRRSV genetic locus codes for the ORF 3 "RKASLSTS" seq uence, and a previously described ORF 4 epitope (Meulenherg, J. J. M., Van Nieuwstadt, A. P,, Van Essen-Zandbergen, A., and Langeveld, J. P. M., 1997, J. Virol. 71, 6061-6067). Sequence analysis identified naturally occurring deletion mutants at this ORF 3/4 site. Phylogenetic analysis showed the pr esence of a highly accurate ORF 3 molecular clock, according to which delet ion mutants and nondeleted viruses evolved at differing speeds. Furthermore , deletion mutants and nondeleted viruses evolved as separate lineages. The se distinctions suggested that deletion mutants were a hitherto unrecognize d subtype of European-type PRRSV. Currently, deletion mutants appear to be outcompeting nondeleted viruses in the field, highlighting the importance o f the porcine antibody response against the minor structural glycoproteins of European-type PRRSV for viral evolution. (C) 2000 Academic Press.