ReviewThe ever-expanding diversity of porcine reproductive and respiratory syndrome virus
Research highlights
▶ The remarkable genetic variation of PRRSV is due to recombination and mutation. ▶ Distinct genotypes indicate prolonged evolutionary divergence prior to emergence. ▶ Phylogeny does not explain biological variation in virulence or immune cross-protection. ▶ The history of pigs determines the history of PRRSV. ▶ Biology of the PRRSV–pig interaction is relevant to other RNA virus–host interactions.
Section snippets
A brief history of PRRS
Porcine reproductive and respiratory syndrome (PRRS) was first recognized as an unexplained reproductive mystery, so-called Mystery Swine Disease, in the midwestern United States in the late 1980s (Keffaber, 1989, Wensvoort et al., 1991). Less well-known was a similar reproductive disease syndrome in northwestern Germany at about the same time that was soon observed in the Netherlands and England (Bischoff et al., 2000, Wensvoort et al., 1991). From these beginnings, PRRS rapidly spread
Viral mechanisms of mutation and recombination
Genetic variation in RNA viruses is assumed to result primarily, if not solely, from RNA polymerase infidelity. This is the simplest explanation for the genetic diversity of PRRSV. Indeed, the calculated rate of PRRSV nucleotide substitution, 4.7–9.8 × 10−2/site/year, is the highest reported so far for an RNA virus (Hanada et al., 2005, Jenkins et al., 2002). More conservative estimates of the PRRSV nucleotide substitution rate are still high (Forsberg, 2005). However, the base incorporation
Relative fitness advantage
According to standard evolutionary theory, viruses that reproduce more rapidly under a given set of conditions will be more successful. Indirect comparisons of PRRSV replication efficacy carried out by in vitro co-culture and measuring viremia in vivo show that there are large differences in replication efficiency among PRRSV isolates (Cho et al., 2006a, Johnson et al., 2004, Kim et al., 2008, Klinge et al., 2009, Murtaugh et al., 2002b, Yuan et al., 1999). Correlation analysis also showed that
Phylogenetic elucidation of PRRSV diversity
Phylogenetic analyses have demonstrated a large evolutionary divergence, of about 40% genetic difference for whole genome sequences, between type 1 and type 2 PRRSV. Such extensive divergence supports the hypothesis that an ancestor of both type 1 and type 2 PRRSV evolved independently in two non-overlapping environments long before PRRSV was identified as a swine virus. The absence of additional genetic lineages in the middle of the long branch linking type 1 and type 2 clusters indicates that
Limitations of PRRSV phylogenetics
Phylogenetic inference through the analysis of nucleic acid sequence information has provided a solid framework in which to order the genetic complexity of PRRSV and to better understand its evolution. However, there are both technical and biological problems that constrain the application of molecular phylogenetics to PRRSV evolution. Technical problems in the interpretation of phylogenetic trees include branches that do not diverge continually, multiple trees with different structures, and
RFLP typing
In 1998, a method of type 2 PRRSV groupings was developed based on restriction fragment length polymorphisms (RFLPs) in MluI, HincII and SacII restriction sites in ORF5 (Wesley et al., 1998). A three-number code was designed to express the results. The key finding was that the widely used vaccine, RespPRRS, now known as Ingelvac MLV (Boehringer Ingelheim), showed a unique pattern of 2-5-2 as compared to all other field isolates.
RFLP typing provided a simple and convenient method of grouping
Perspectives on PRRSV classification methods
Continuous mutational change in PRRSV genomes within a pig and during prolonged transmission among pigs in a commercial swine herd facilitates gradual evolution with no clear boundary that would differentiate one virus as distinctly different from another virus. Therefore, the lack of stable viral genomes within type 1 and type 2 PRRSV limits the utility of simple classification schemes that do not easily accommodate the regular appearance of new genotypes whose characteristics cannot be
Biological implications of diversity on PRRSV evolution
The PRRSV population structure in the field today consists of two genetically separate families of PRRSV that show no evidence of intermediate forms or recombinatorial compatibility besides type 1 and type 2 (Fig. 3; Murtaugh et al., 2002b, Yuan et al., 1999). Therefore, PRRSV was present as two distinct and geographically isolated genotypes when it was discovered. The discovery of PRRSV coincided with large-scale changes in swine rearing and breeding, which occurred in Europe and North America
The future of PRRS
PRRS is a devastating disease with significant economic consequences to swine producers and consumers. Therefore, predicting the evolutionary trajectory of PRRSV is more than an academic exercise. If fully comprehended it would have the potential to improve swine management through reduction of viral genetic variation, increased uniformity of immunological protection, and more consistent disease control. Improved knowledge of the mechanisms of diversification, and biological drivers of
Acknowledgements
The work and ideas presented here were generated in part with support by the PRRS Coordinated Agricultural Project funded through USDA Cooperative State Research, Education and Extension Service, grant numbers 2004-35605-14197 and 2008-55620-19132, the Strategic Research Theme of Infection and Immunology from The University of Hong Kong, the Polish Ministry of Science and Higher Education no. NN308265136, EU FP7 grant no. 245141, and EU COST Action FA902.
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