Infection of porcine alveolar macrophages with recombinant chimeric porcine reproductive and respiratory syndrome virus: effects on cellular gene transcription and virus growth.
Porcine reproductive and respiratory syndrome virus (PRRSV) genetic determinants affecting the response of the host primary target cell, the macrophage, to infection are yet to be defined. Here we have used recombinant viruses encompassing ORF 1A to identify PRRSV determinants associated with growth and modulation of pro- and anti-inflammatory cytokine expression in primary pulmonary alveolar macrophages (PAMs) cultures. Three genomic chimeras encompassing ORF 1A of PRRSV live attenuated vaccine Prime Pac (LAV SP) in the genetic background of pathogenic strain NVSL 97-7895 (FL12v) were characterized in vitro. Unlike parental viruses, two of the recombinant viruses encompassing the area of the genome encoding for NSP2 to NSP8 showed reduced growth in PAM cultures. The effect of virus infections on gene activation was studied for 25 immunomodulatory cellular genes in PAMs at 24 and 48h post-infection (hpi). Steady state mRNA levels in PAMs infected with recombinant and LAV SP viruses were compared to levels observed in cells infected with parental virus FL12v. Recombinant viruses induced patterns of transcriptional activation differing from patterns induced by parental FL12v, suggesting a regulatory role of PRRSV ORF1A on PAM gene expression.