39e94cfe02ae9932c3ceae619c6c1527  VIE_a2024v10n1.pdf
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Title:           Selection of viral variants with enhanced transmission and reduced neutralization susceptibility alongside lateral introductions may explain the persistence of porcine reproductive and respiratory syndrome virus in vaccinated breeding herds
Subject:         DOI: https://doi.org/10.1093/ve/veae041
Virus Evolution, 10, 1, xx xx xxxx.
Abstract: This study investigates the long-term evolutionary dynamics of porcine reproductive and respiratory syndrome virus (PRRSV-1) in an endemically infected and vaccinated pig herd. Over a one year and a half period, piglets from seven farrowing batches in a 300-sow PRRSV-vaccinated farm were monitored from birth to nine weeks of age by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Eighty-five PRRSV-positive samples were subjected to whole genome sequencing (Illumina Miseq), and 251 samples to open reading frame 5 (ORF5) sequencing. Farm-specific PRRSV variants’ impact on anti-PRRSV antibodies was evaluated using enzyme-linked immunosorbent and neutralizing antibody assays. The replication kinetics and cytokine inhibition capabilities (IFN-α and TNF-α) of these variants were assessed in porcine alveolar macrophages. The study revealed fluctuating PRRSV-1 incidences in farrowing units and nurseries, attributed to two key evolutionary events: an escape variant emergence and a lateral introduction of a new strain. Initially, strain 1 variant α was swiftly replaced within weeks by variant 1β (99.5 per cent genomic similarity), with twenty-five amino acid mutations, primarily in nsp1α, GP2, GP3, and GP5, including an additional glycosylation site and a deletion downstream the neutralization epitope of GP5. This shift to 1β correlated with increased incidence in nurseries and higher viral loads, with sera from 1α-exposed animals showing reduced neutralization against 1β. Consistently for in vitro assays, variant 1β demonstrated enhanced replication in porcine alveolar macrophages but no difference regarding IFN-α or TNF-α responses. Later, a new strain (strain 2, 83.3 per cent similarity to strain 1) emerged and led to incidence resurgence because of the low cross reactivity with the previous antibodies. The study highlights PRRSV’s rapid adaptability and challenges in controlling its spread, underscoring the necessity for more effective vaccines and eradication approaches.
Keywords:        PRRSV; endemic; viral evolution; persistence; vaccination.
Author:          Hepzibar Clilverd
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     Item: 
      Title: Selection of viral variants with enhanced transmission and reduced neutralization susceptibility alongside lateral introductions may explain the persistence of porcine reproductive and respiratory syndrome virus in vaccinated breeding herds
      Children: 
       Item: 
        Title: 1. Introduction
       Item: 
        Title: 2. Materials and methods
        Children: 
         Item: 
          Title: 2.1 Study farm and follow-up chronology
         Item: 
          Title: 2.2 PRRSV detection
         Item: 
          Title: 2.3 PRRSV isolation
         Item: 
          Title: 2.4 Sequencing
         Item: 
          Title: 2.5 Phylogenetic and evolutionary analysis
         Item: 
          Title: 2.6 Adaptation to grow on MARC-145 cells and viral production in PAM
         Item: 
          Title: 2.7 Serological analyses (enzyme-linked immunosorbent assay and viral neutralization test)
         Item: 
          Title: 2.8 Viral replication kinetics
         Item: 
          Title: 2.9 Attachment of different viral variants to PAM
         Item: 
          Title: 2.10 Inhibition of IFN-α and TNF-α
         Item: 
          Title: 2.11 Statistical analyses
       Item: 
        Title: 3. Results
        Children: 
         Item: 
          Title: 3.1 PRRSV infection dynamics in the farm and VTEs
         Item: 
          Title: 3.2 Phylogenetic and recombination analyses and viral variant characterization
         Item: 
          Title: 3.3 Serological analyses
         Item: 
          Title: 3.4 Replication kinetics of variants 1α and 1β in PAM
         Item: 
          Title: 3.5 Attachment of variants 1α and 1β on PAM
         Item: 
          Title: 3.6 Inhibition of poly I:C induced IFN-α and TNF-α
       Item: 
        Title: 4. Discussion
       Item: 
        Title:  Data availability
       Item: 
        Title: Supplementary data
       Item: 
        Title: Acknowledgements
       Item: 
        Title: Funding
       Item: 
        Title: Conflict of interest:
       Item: 
        Title: References
   Info: 
    Title: Selection of viral variants with enhanced transmission and reduced neutralization susceptibility alongside lateral introductions may explain the persistence of porcine reproductive and respiratory syndrome virus in vaccinated breeding herds
    Author: Hepzibar Clilverd
    Subject: DOI: https://doi.org/10.1093/ve/veae041
Virus Evolution, 10, 1, xx xx xxxx.
Abstract: This study investigates the long-term evolutionary dynamics of porcine reproductive and respiratory syndrome virus (PRRSV-1) in an endemically infected and vaccinated pig herd. Over a one year and a half period, piglets from seven farrowing batches in a 300-sow PRRSV-vaccinated farm were monitored from birth to nine weeks of age by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Eighty-five PRRSV-positive samples were subjected to whole genome sequencing (Illumina Miseq), and 251 samples to open reading frame 5 (ORF5) sequencing. Farm-specific PRRSV variants’ impact on anti-PRRSV antibodies was evaluated using enzyme-linked immunosorbent and neutralizing antibody assays. The replication kinetics and cytokine inhibition capabilities (IFN-α and TNF-α) of these variants were assessed in porcine alveolar macrophages. The study revealed fluctuating PRRSV-1 incidences in farrowing units and nurseries, attributed to two key evolutionary events: an escape variant emergence and a lateral introduction of a new strain. Initially, strain 1 variant α was swiftly replaced within weeks by variant 1β (99.5 per cent genomic similarity), with twenty-five amino acid mutations, primarily in nsp1α, GP2, GP3, and GP5, including an additional glycosylation site and a deletion downstream the neutralization epitope of GP5. This shift to 1β correlated with increased incidence in nurseries and higher viral loads, with sera from 1α-exposed animals showing reduced neutralization against 1β. Consistently for in vitro assays, variant 1β demonstrated enhanced replication in porcine alveolar macrophages but no difference regarding IFN-α or TNF-α responses. Later, a new strain (strain 2, 83.3 per cent similarity to strain 1) emerged and led to incidence resurgence because of the low cross reactivity with the previous antibodies. The study highlights PRRSV’s rapid adaptability and challenges in controlling its spread, underscoring the necessity for more effective vaccines and eradication approaches.
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Virus Evolution, 10, 1, xx xx xxxx.
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