Refining PRRSV-2 genetic classification based on global ORF5 sequences and investigation of their geographic distributions and temporal changes

Authors: YIM-IM, WANNARAT - Iowa State University; Anderson, Tavis; PAPLOSKI, IGOR - University Of Minnesota; VANDERWAAL, KIMBERLY - University Of Minnesota; GAUGER, PHILLIP - Iowa State University; KRUEGER, KAREN - Iowa State University; SHI, MANG - Sun Yat-Sen University; MAIN, RODGER - Iowa State University; ZHANG, JIANQIANG - Iowa State University

Submitted to: Microbiology Spectrum
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/1/2023
Publication Date: 11/7/2023
Citation: Yim-Im, W., Anderson, T.K., Paploski, I.A., Vanderwaal, K., Gauger, P.C., Krueger, K., Shi, M., Main, R., Zhang, J. 2023. Refining PRRSV-2 genetic classification based on global ORF5 sequences and investigation of their geographic distributions and temporal changes. Microbiology Spectrum. https://doi.org/10.1128/spectrum.02916-23.
DOI: https://doi.org/10.1128/spectrum.02916-23

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 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, 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 1989 and 2021 using 82,237 sequences. These data revealed continual turnover of genetic clades, with eleven lineages, 21 sublineages, and 5 groups with L1C necessary to define PRRSV-2 genetic diversity. This study refined PRRSV-2 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 (PRRSV) is an important swine pathogen affecting the global swine industry. The first ORF5-based genetic lineage classification system describing global PRRSV-2 genetic diversity was introduced a decade ago. Although a refinement on the lineage 1 classification has recently been attempted in the U.S., PRRSV-2 phylogenetic classification system at international levels has not been thoroughly evaluated and updated after 2010. In this study, based on analysis of 82,237 global ORF5 sequences reported during 1989–2021, we classified PRRSV-2 into eleven genetic lineages (L1'L11) and 21 sublineages (L1A'L1F, L1H'L1J, L5A'L5B, L8A'L8E, and L9A'L9E). The proposed classification system is flexible for growth if additional lineages, sublineages, or more granular classifications are needed. Further classification of the sublineage L1C into five groups (L1C.1'L1C.5) with L1C.5 corresponding to recently emerged L1C variant strains is a stellar example to meet epidemiological investigation needs. Comparison between restriction fragment length polymorphism (RFLP) typing and phylogenetic classification revealed the inaccuracy of using RFLP to determine PRRSV-2 genetic relatedness in most scenarios. Genetic homology of six commercial PRRSV-2 vaccines to each lineage/sublineage and detection frequency of vaccine-like viruses were determined. Global geographic distribution of each lineage/sublineage was presented. Temporal dynamic changes of PRRSV-2 in the U.S. during 1989–2021 were investigated by analyzing 73,092 ORF5 sequences. In summary, this study refined PRRSV-2 ORF5-based phylogenetic classification and investigated the geographic distribution and temporal changes of PRRSV-2 at the lineage/sublineage levels. The refined classification system and molecular epidemiology data in this study will be invaluable for future characterization of PRRSV-2.