Refining genetic classification of global porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) and investigating their geographic and temporal distributions

Authors: YIM-IM, WANNARAT - Iowa State University; Anderson, Tavis; BOHMER, JAN - Society Of Innovative Veterinary Diagnostics (IVD GMBH); BALIELLAS, JORDI - Pig Sanitation Group (GSP); STADEJEK, TOMASZ - Warsaw University Of Life Sciences; GAUGER, PHILLIP - Iowa State University; KRUEGER, KAREN - Iowa State University; VERMEULEN, CORNELIS - Gd Animal Health Service; BUTER, RIANNE - Gd Animal Health Service; KAZLOUSKI, ALIAKSANDR - Vitebsk State Academy Of Veterinary Medicine; AN, TONGQING - Chinese Academy Of Agricultural Sciences; ZHANG, JIANQIANG - Iowa State University

Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/25/2025
Publication Date: 2/3/2025
Citation: Yim-Im, W., Anderson, T.K., Bohmer, J., Baliellas, J., Stadejek, T., Gauger, P.C., Krueger, K.M., Vermeulen, C., Buter, R., Kazlouski, A., An, T., Zhang, J. 2025. Refining genetic classification of global porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) and investigating their geographic and temporal distributions. Veterinary Microbiology. https://doi.org/10.1016/j.vetmic.2025.110413.
DOI: https://doi.org/10.1016/j.vetmic.2025.110413

Interpretive Summary: Understanding how Porcine reproductive and respiratory syndrome virus (PRRSV) are changing in swine in a timely manner is critical to reduce disease burden in pigs and reduce the risk of novel viruses spreading through populations. The genetic makeup of PRRSV continually changes, yet there are no established methods to report significant genetic changes, specifically, in the regularly sequenced viral surface protein gene, open reading frame 5 (ORF5). Previous reporting of new type 1 PRRSV ORF5 genes in swine relied on names and terms used by individual research scientists that provided little insight into the biology of the virus. Using a large dataset of swine ORF5 genetic sequences and available whole genome sequence data, we developed an adaptable naming system that uses measurable criteria to define historical and contemporary evolutionary patterns of PRRSV ORF5 genes. Using this system, we quantified the global genetic diversity of PRRSV ORF5 between 1991 and 2023 using 10,446 sequences. These data revealed continual turnover of genetic clades, with four lineages (L1'L4) and L1 including 18 sublineages (L1.1 to L1.18) necessary to define PRRSV-type 1 genetic diversity. This study refined PRRSV-type 1 ORF5-based phylogenetic classification and demonstrated how diversity varied geographically and temporally. The refined classification system and the molecular epidemiology data in this study will aid and improve our ability to control PRRSV through identifying field-relevant virus strains and spatial and temporal changes in major groups of ORF5 genes circulating in pigs.

Technical Abstract: Porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) primarily circulates in Europe but is also detected in North America and Asia. Based on ORF5 sequences, previous studies classified PRRSV-1 into four subtypes. Subtype 1 was further classified into 12 clades (A-L) or into three lineages with lineage 1 including clades 1A'1G and lineage 3 including clades 3A'3G, but the systems are inconsistent and have not been adopted. In this study, we proposed a statistically supported PRRSV-1 genetic classification system based on 10,446 global PRRSV-1 ORF5 sequences spanning 1991'2023. We replaced the colloquial “subtype” designation with “lineage” to reflect evolutionary history and, subsequently, PRRSV-1 was classified into four lineages (L1'L4) with L1 including 18 sublineages (L1.1 to L1.18). The proposed classification system is flexible and may be amended if additional lineages, sublineages, or more granular classifications are needed to reflect contemporary PRRSV-1 detections and evolution. Geographic distributions of PRRSV-1 at lineage and sublineage levels and temporal dynamic changes in some countries were quantified. Classification and ORF5 nucleotide identity of six commercial PRRSV-1 vaccines to each lineage and sublineage and detection frequency of vaccine-like viruses were determined. The phylogenies based on whole-genome and ORF5 sequences demonstrated slightly different tree topologies due to recombination. Recombination of PRRSV-1 was observed at intra-sublineage and inter-sublineage levels. A set of reference sequences representing the refined classification is available for future diagnostic and epidemiological applications. This study provides a benchmark delineating current genetic diversity of PRRSV-1 and the refined classification system can be used to characterize the genetic and phenotypic evolution of PRRSV-1.