Differential immunity in pigs with high and low responses to porcine reproductive and respiratory syndrome virus infection.

One hundred Hampshire x Duroc cross-bred pigs (HD) and 100 NE Index line (I) pigs were infected with porcine reproductive and respiratory syndrome (PRRS) virus and evaluated for resistance/susceptibility. Controls (100/line) were uninfected littermates to the infected pigs. Viremia, change in weight (WTdelta), and rectal temperature at 0, 4, 7, and 14 d postinfection were recorded. Lung, bronchial lymph node (BLN), and blood tissue were collected at necropsy (14 d postinfection). The first principal component from principal component analyses of all variables was used to rank the pigs for phenotypic response to PRRS virus. Low responders (low PRRS burden) had high WTdelta, low viremia, and few lung lesions; high responders (high PRRS burden) had low WTdelta, high viremia, and many lesions. The RNA was extracted from lung and BLN tissue of the 7 highest and 7 lowest responders per line and from each of their littermates. Expression of 11 innate and T helper 1 immune markers was evaluated with cDNA in a 2 x 2 x 2 factorial design. Significant upregulation in lung, lymph, or both of infected pigs relative to controls occurred for all but one gene. Expression differences were greater in HD than I pigs. Significant downregulation for certain immune genes in low pigs, relative to littermate controls, was detected in lung and BLN, particularly in line I. Serum levels of the immune cytokines affirmed the gene expression differences. High preinfection serum levels of IL 8 were significantly associated with PRRS virus-resistant, low pigs. After infection, low expression of interferon gamma in cDNA and in serum was also correlated with PRRS virus resistance. Important genetic associations were revealed for fine mapping of candidate genes for PRRS virus resistance and determining the causative alleles.