Tracing the origin of the novel PRRSV-2 L1C-1-4-4 variant

Most atypical losses from the Midwestern U.S. PRRS outbreaks in 2020-21 were caused by the same novel variant, L1C-1-4-4.


By Nakarin Pamornchainavakul, Mariana Kikuti, Igor A. D. Paploski, Dennis N. Makau, Albert Rovira, Cesar A. Corzo and Kimberly VanderWaal, University of Minnesota

National Hog Farmer - May 10, 2022


Currently, numerous breeding and growing pig herds in the Midwestern United States have suffered from massive porcine reproductive and respiratory syndrome outbreaks caused by the novel PRRSV-2 variant, L1C-1-4-4. Viruses belonging to this variant have highly similar genetic material, i.e. > 98% nucleotide identity in both open reading frame 5 (ORF5) gene and whole genome1. Although this variant is part of sub-lineage 1C (L1C)3, questions remain on how this variant rapidly spread and lead to atypical production losses.


Like other RNA viruses, the high mutation rate of PRRSV-2 allows it to adapt, survive and sometimes become more virulent. Previous studies demonstrate that virulence and antigenicity of PRRSV-2 is determined by several regions throughout the genome5,6. At the same time, most efforts to analyze PRRSV-2 sequences focus only the ORF5 gene, which represents just 4% of the genome. Thus, analyzing whole genome sequences (WGSs) of the L1C-1-4-4 variant is a first crucial step to understand how this virus differs from other circulating variants.


Inferring a virus's evolutionary origin from whole genomes is complicated due to the occurrence of recombination, which is an evolutionary mechanism by which genomic fragments are exchanged between viruses (Figure 1A). Such events contribute to the genetic diversity in the virus population and potentially lead to rapid changes in a virus's genetic makeup and, potentially, its phenotype. Moreover, recombination can result in distinct evolutionary histories amongst different recombined genomic fragments, which makes WGS-based analysis hard to interpret.


We screened a set of PRRSV-2 whole genomes for recombination, including the novel L1C-1-4-4 variant (n = 19) and other isolates collected in the United States over the past two decades (n = 232). Sequences were classified into lineages (L1-9) and sub-lineages (L1A-H) according to shared ancestry in the ORF5 gene. Three distinct WGS fragments were then used to estimate the virus's evolutionary history and frequency of ancestral inter-(sub)lineage recombination.


The analyses confirmed...


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