Knockout of SIGLEC1 in pigs reduces porcine reproductive and respiratory syndrome-1 (PRRSV-1) virus infection in primary macrophage cultures, but not in pigs

Siglec-1, also known as sialoadhesin (Sn) or CD169, is a product of the SIGLEC1 gene. A large body of work performed on cell culture systems concludes that Siglec-1 is a primary receptor for porcine reproductive and respiratory syndrome virus (PRRSV) isolates in the genotype 1 or PRRSV-1 group. In this study, primary cultures of PAMs from SIGLEC-1 knockout (KO) pigs showed resistance to infection using both PRRSV-1 and PRRSV-2 isolates, which is consistent with previous observations. However, infection of KO and WT pigs with a PRRSV-1 isolate, SD01-08, resulted in viremia in both groups. Interestingly, virus nucleic acid levels in sera were significantly greater in the KO pigs at 21 and 28 days after infection. Mean virus load, calculated as area under the viremia curve over the infection period, was also significantly greater for the KO group. At the level of the pig, Siglec-1 as a receptor for PRRSV may not be biologically relevant. The increased viremia observed for the KO pigs may reflect a role for Siglec-1 in the regulation of the immune response to PRRSV-1.