Regulation of immune responses and genetic resistance to infectious viral diseases is an area of concern for human and swine. Porcine Reproductive and Respiratory Syndrome (PRRS) is caused by the PRRS virus, an enveloped, single-stranded positive-sense RNA virus. When present in a herd, PRRSV causes increased abortions, stillbirths, mummies and chronic respiratory problems in pigs resulting in >$560 million losses in the US each year 84
. As an RNA virus with an evolving genome, PRRSV is particularly problematic due to slow development of protective immunity to homologous challenge and lack of protection against heterologous virus challenge. Thus it is a major target for swine research; information gained from swine studies will inform human infectious disease studies, particularly for analyses of viral persistence and of factors relevant to prevention of congenital and seminal transmission pathways.
Major efforts are underway to identify factors regulating PRRSV immunity, persistence and transmission. Tests involve probing local mucosal anti-viral responses (Petry et al., submitted). Detailed cellular analyses have assessed gene and protein expression. As with human disease studies analyses of cultured cells, e.g., infected MARC cells 85
, swine macrophages 86, 87
, or samples from infected pigs 88
, have expanded our knowledge of the impact of timing and level of viral infection on gene expression and pathway involvement. Future work will determine whether RNAi approaches will be effective. More detailed gene expression analyses are underway using long oligo and Affymetrix arrays, testing both pooled and individual animal samples, as well as mucosal samples at death. An important issue is the timing of mucosal sample collection. Results can be disappointing if mucosal samples are collected only after viral levels begin to resolve. The peak of anti-viral immunity (and relevant gene expression) may be much earlier; however, that may be at a time when the actual viral levels may be difficult to evaluate and thus complicate comparative analyses. Therefore, it is important to affirm preliminary results with hypothesis driven repeated analyses and with translation of gene expression and array results into protein expression data.
Genetic variation does exist in resistance/susceptibility to viral infections and has been proven for swine resistance/susceptibility to PRRS 87, 89
. Although to date there is limited knowledge of host genes determining PRRSV resistance; some candidate genes have been identified (Petry et al., submitted). More detailed studies are required to determine whether naturally disease resistant pigs can be identified and why do [some] pigs stay healthy even with PRRS? What set of factors (detailed phenotype) truly correlate with lower PRRSV burden? What is the potential for sampling peripheral blood cells, serum or saliva for preinfection predictive studies of genetically determined virus resistance phenotype?
An international PRRS Genomics Consortium, of university, government, and company based scientists, has been established to assess host genetics of PRRS resistance/susceptibility. The goal is to develop a large, publicly available disease sample and dataset from thousands of pigs from relevant commercial lines infected with PRRSV and from which a detailed phenotype have been collected. Access to samples will be dependent on data sharing. The end user performs his/her analysis on the appropriate sample and returns the data to the consortium. It is hoped that the data generated by the Consortium will verify the genetic variation in pigs responding to PRRSV infection, will reveal factors influencing health, survivability and growth, and will identify the relative importance of different phenotypes, and their heritability, in predicting responses to PRRSV infection. Overall this data should enable breeders to produce healthier pigs with improved resistance to PRRSV and help animal health companies to develop improved vaccines and alternative anti-PRRSV therapeutics. This data should help identify new critical control factors in human responses to viral infections.