Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) depends on the CD163 receptor to establish infection. Although CD163-knockout (KO) pigs exhibit resistance to PRRSV-related respiratory disease, their reproductive performance following viral challenge has not been adequately assessed. In this study, we assessed the resistance of CD163-KO gilts and sows to PRRSV, focusing on both systemic infection and vertical transmission, by performing two independent challenge experiments: one in nulliparous gilts and another in late-gestation dams, all inoculated with a NADC30-like PRRSV strain. In nulliparous gilts, wild-type (WT) animals developed severe viremia, fever, viral shedding, seroconversion, and high tissue viral loads, whereas CD163-KO gilts remained completely asymptomatic with undetectable viral RNA and no antibody response throughout the 21-day observation period. In WT pregnant dams, PRRSV was transmitted to the vast majority of fetuses. Conversely, all CD163-KO dams remained clinically healthy, and their viable fetuses uniformly tested negative for viral antigen, irrespective of fetal CD163 genotype. These results unequivocally demonstrate that maternal CD163 deficiency completely abrogates both PRRSV replication and transplacental spread, preserving reproductive health and fetal viability, thereby confirming that CD163 is indispensable for all major manifestations of PRRSV infection and highlighting the strong potential of CD163-edited pigs for disease control in the pig industry.