Host genetic differences in viral load (VL) and weight gain (WG) during challenge were assessed for five trials of ~200 commercial crossbred piglets each, all from different commercial suppliers. Piglets were experimentally infected with porcine reproductive and respiratory syndrome virus (PRRSV) isolate KS-2006-72109 in order to validate the effects of a SNP previously identified on SSC4 (WUR10000125), whereby AB individuals had increased WG and reduced VL when experimentally infected with PRRSV isolate NVSL-97-7895. VL was defined as the area under the curve of logged viremia from 0-21 dpi. WG was defined as the weight gained from 0-42 dpi. The SNP effects on VL and WG were assessed. AB individuals had higher WG and lower VL than AA individuals, suggesting this marker may be useful for genetic selection of pigs for increased resistance or reduced susceptibility to PRRSV isolates that differ genetically and possibly pathogenically.