Porcine reproductive and respiratory syndrome virus replication and quasispecies evolution in pigs that lack adaptive immunity.

The replication of porcine reproductive and respiratory syndrome virus (PRRSV) was studied in a line of pigs possessing a severe combined immunodeficiency (SCID). Real-time RT-PCR revealed a unique course of infection for the SCID group. During the course of infection, viremia was initially significantly lower than normal littermates, but by 21 days was significantly elevated. Deep sequencing of the viral structural genes at days 11 and 21 identified seven amino acid substitutions in both normal and SCID pigs. The most significant change was a W99R substitution in GP2, which was present in the inoculum at a frequency of 35%, but eventually disappeared from all pigs regardless of immune status. Therefore, amino acid substitutions that appear during acute infection are likely the result of the adaptation of the virus to replication in pigs and not immune selection.