Elsevier

Virus Research

Volume 154, Issues 1–2, December 2010, Pages 18-30
Virus Research

Review
The ever-expanding diversity of porcine reproductive and respiratory syndrome virus

https://doi.org/10.1016/j.virusres.2010.08.015Get rights and content

Abstract

Porcine reproductive and respiratory syndrome (PRRS) virus appeared 20 years ago as the cause of a new disease in swine. Today PRRS is the most significant swine disease worldwide in spite of intensive immunological interventions. The virus showed remarkable genetic variation with two geographically distinct genotypes at the time of its discovery, indicating the possibility of prolonged evolutionary divergence prior to its appearance as a swine pathogen. Since then, both type 1 and type 2 have spread geographically, radiated genetically, and acquired new phenotypic characteristics, especially increased virulence. Here, we explore various hypotheses that might account for rapid expansion and diversification of PRRSV, including mechanisms specific to PRRSV and other arteriviruses, cellular modification processes, and immunological selection. Phylogenetic analysis of PRRSV has provided a broadly applicable means to relate diverse isolates, but it does not explain biological variation in virulence or immunological cross-protection. We present other methods of classification and review their limitations. Major questions about PRRSV remain unanswered despite intensive investigation, suggesting that the interaction of PRRSV with pigs involves novel biological processes that may be relevant to other RNA virus and host interactions.

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.

References (134)

  • S. Indik et al.

    Genetic variability of PRRS virus in Austria: consequences for molecular diagnostics and viral quantification

    Vet. Microbiol.

    (2005)
  • W. Johnson et al.

    Pathogenic and humoral immune responses to porcine reproductive and respiratory syndrome virus (PRRSV) are related to viral load in acute infection

    Vet. Immunol. Immunopathol.

    (2004)
  • S.Y. Kang et al.

    Molecular characterization of PL97-1, the first Korean isolate of the porcine reproductive and respiratory syndrome virus

    Virus Res.

    (2004)
  • W.I. Kim et al.

    Effect of genotypic and biotypic differences among PRRS viruses on the serologic assessment of pigs for virus infection

    Vet. Microbiol.

    (2007)
  • K. Li et al.

    Isolation of lactate dehydrogenase-elevating viruses from wild house mice and their biological and molecular characterization

    Virus Res.

    (2000)
  • O.J. Lopez et al.

    Role of neutralizing antibodies in PRRSV protective immunity

    Vet. Immunol. Immunopathol.

    (2004)
  • M.H. Malim et al.

    HIV-1 accessory proteins—ensuring viral survival in a hostile environment

    Cell Host Microbe

    (2008)
  • J.J. Meulenberg et al.

    Lelystad virus, the causative agent of porcine epidemic abortion and respiratory syndrome (PEARS), is related to LDV and EAV

    Virology

    (1993)
  • R.M. Molina et al.

    Immune response against porcine reproductive and respiratory syndrome virus during acute and chronic infection

    Vet. Immunol. Immunopathol.

    (2008)
  • M.B. Oleksiewicz et al.

    Emergence of porcine reproductive and respiratory syndrome virus deletion mutants: correlation with the porcine antibody response to a hypervariable site in the ORF 3 structural glycoprotein

    Virology

    (2000)
  • S. Pesch et al.

    New insights into the genetic diversity of European porcine reproductive and respiratory syndrome virus (PRRSV)

    Vet. Microbiol.

    (2005)
  • P. Pesente et al.

    Phylogenetic analysis of ORF5 and ORF7 sequences of porcine reproductive and respiratory syndrome virus (PRRSV) from PRRS-positive Italian farms: a showcase for PRRSV epidemiology and its consequences on farm management

    Vet. Microbiol.

    (2006)
  • A. Pitkin et al.

    Use of a production region model to assess the airborne spread of porcine reproductive and respiratory syndrome virus

    Vet. Microbiol.

    (2009)
  • C. Prieto et al.

    Influence of time on the genetic heterogeneity of Spanish porcine reproductive and respiratory syndrome virus isolates

    Vet. J.

    (2009)
  • R.R. Rowland et al.

    The evolution of porcine reproductive and respiratory syndrome virus: quasispecies and emergence of a virus subpopulation during infection of pigs with VR-2332

    Virology

    (1999)
  • T. Ait-Ali et al.

    Innate immune responses to replication of porcine reproductive and respiratory syndrome virus in isolated swine alveolar macrophages

    Viral Immunol.

    (2007)
  • J.S. Albin et al.

    Interactions of host APOBEC3 restriction factors with HIV-1 in vivo: implications for therapeutics

    Expert Rev. Mol. Med.

    (2010)
  • T.J. Alexander et al.

    Medicated early weaning to obtain pigs free from pathogens endemic in the herd of origin

    Vet. Rec.

    (1980)
  • T.Q. An et al.

    Origin of highly pathogenic porcine reproductive and respiratory syndrome virus, China

    Emerg. Infect. Dis.

    (2010)
  • I.H. Ansari et al.

    Influence of N-linked glycosylation of porcine reproductive and respiratory syndrome virus GP5 on virus infectivity, antigenicity, and ability to induce neutralizing antibodies

    J. Virol.

    (2006)
  • L. Batista et al.

    Genetic diversity and possible avenues of dissemination of PRRSV in two geographic regions of Mexico

    J. Swine Health Prod.

    (2004)
  • C. Bischoff et al.

    History, occurrence, dynamics and current status of PRRS in Europe

    Vet. Res.

    (2000)
  • K.N. Bishop et al.

    APOBEC-mediated editing of viral RNA

    Science

    (2004)
  • S. Carman et al.

    Assessment of seropositivity to porcine reproductive and respiratory syndrome (PRRS) virus in swine herds in Ontario—1978 to 1982

    Can. Vet. J.

    (1995)
  • S.H. Cha et al.

    Instability of the restriction fragment length polymorphism pattern of open reading frame 5 of porcine reproductive and respiratory syndrome virus during sequential pig-to-pig passages

    J. Clin. Microbiol.

    (2004)
  • C.C. Chang et al.

    Evolution of porcine reproductive and respiratory syndrome virus during sequential passages in pigs

    J. Virol.

    (2002)
  • J.G. Cho et al.

    Evaluation of the effects of animal age, concurrent bacterial infection, and pathogenicity of porcine reproductive and respiratory syndrome virus on virus concentration in pigs

    Am. J. Vet. Res.

    (2006)
  • J.G. Cho et al.

    The impact of animal age, bacterial coinfection, and isolate pathogenicity on the shedding of porcine reproductive and respiratory syndrome virus in aerosols from experimentally infected pigs

    Can. J. Vet. Res.

    (2006)
  • J. Christopher-Hennings et al.

    Detection of porcine reproductive and respiratory syndrome virus in boar semen by PCR

    J. Clin. Microbiol.

    (1995)
  • J.L. Corn et al.

    Pathogen exposure in feral swine populations geographically associated with high densities of transitional swine premises and commercial swine production

    J. Wildl. Dis.

    (2009)
  • S. Dea et al.

    Antigenic variability among North American and European strains of porcine reproductive and respiratory syndrome virus as defined by monoclonal antibodies to the matrix protein

    J. Clin. Microbiol.

    (1996)
  • E. Domingo et al.

    Basic concepts in RNA virus evolution

    Faseb J.

    (1996)
  • K.S. Faaberg et al.

    Predicted RNA folding suggests PRRSV major and heteroclite subgenomic transcripts result from polymerase switching at unpaired nucleotides

  • Y. Fang et al.

    Diversity and evolution of a newly emerged North American Type 1 porcine arterivirus: analysis of isolates collected between 1999 and 2004

    Arch. Virol.

    (2007)
  • R.H. Foote

    The history of artificial insemination: selected notes and notables

    J. Anim. Sci.

    (2002)
  • R. Forsberg

    Divergence time of porcine reproductive and respiratory syndrome virus subtypes

    Mol. Biol. Evol.

    (2005)
  • D.L. Foss et al.

    Adjuvant danger signals increase the immune response to porcine reproductive and respiratory syndrome virus

    Viral Immunol.

    (2002)
  • R. Franca et al.

    APOBEC deaminases as cellular antiviral factors: a novel natural host defense mechanism

    Med. Sci. Monit.

    (2006)
  • E. Giuffra et al.

    The origin of the domestic pig: independent domestication and subsequent introgression

    Genetics

    (2000)
  • R. Goldbach et al.

    RNA viral supergroups and the evolution of RNA viruses

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