The present disclosure provides compositions and methods for decreasing permissiveness to infection by PRRSV. The methods involve inserting peptides or oligopeptides into the CD163 SRCR domain 5 to disrupt the protein structure and thereby prevent PRRSV infection. The deletion of the exon 13 region of PSTII eliminates infection. The replacement of cysteine residues with alanines in SRCR5 as a means to disrupt disulfide bond formation. The final method is the deletion of, or amino acid substitution within the SRCR4-5 interdomain region.