{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:07:53Z","timestamp":1788959273725,"version":"build-2803163510"},"reference-count":141,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Peripheral blood mononuclear cells (PBMCs) are the most immunologically active and readily accessible fraction of whole blood, and they initiate host immune responses following infection and vaccination. Since PBMC transcriptomes capture diverse host\u2013pathogen interactions, they offer a promising tool to uncover the genetic drivers of viral resistance and tolerance. As a detailed case study of this principle, we examine porcine reproductive and respiratory syndrome (PRRS), which remains one of the most economically important viral diseases of swine worldwide. Following PRRS virus (PRRSV) exposure, pigs rely on two complementary defense strategies: resistance, the capacity to limit viral replication, and tolerance, the capacity to sustain performance despite infection. Since resistance and tolerance phenotypes are difficult to measure directly through experimental challenge, indirect immune-trait measurements collected after vaccination offer a practical alternative. Most transcriptomic studies of the host response to PRRSV have focused on respiratory tissues, reflecting the virus\u2019s tropism for pulmonary macrophages. However, intramuscularly delivered modified-live PRRSV vaccine reaches the bloodstream, bypassing the lung, so PBMCs, as the frontline defense system, mount the earliest measurable innate response. This review synthesizes the current literature on PBMC transcriptome models for deciphering innate resistance and tolerance to viral disease, using PRRS as our principal worked example; presents our own approach to profiling PBMCs after PRRSV vaccination; and outlines how the field has advanced since the original candidate-gene and QTL studies of the 2010s, including the recent FDA approval of the first CD163 gene-edited PRRSV-resistant pig line, and the emergence of single-cell and multi-tissue PBMC atlases, before considering how the same PBMC-based approach could extend to other host\u2013virus interactions.<\/jats:p>","DOI":"10.3390\/v18090994","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:26:11Z","timestamp":1788956771000},"page":"994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral Blood Mononuclear Cell Transcriptomics in Porcine Reproductive and Respiratory Syndrome: A Window into Innate Immune Resistance and Tolerance to Viral Disease"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1979-9652","authenticated-orcid":false,"given":"Md Aminul","family":"Islam","sequence":"first","affiliation":[{"name":"Department of Animal Breeding and Husbandry, Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany"},{"name":"Immunogenomics and Alternative Medicine Laboratory, Department of Medicine, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh"},{"name":"Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Neuhoff","sequence":"additional","affiliation":[{"name":"Department of Animal Breeding and Husbandry, Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren Julia","family":"Pr\u00f6ll","sequence":"additional","affiliation":[{"name":"Department of Animal Breeding and Husbandry, Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Gro\u00dfe-Brinkhaus","sequence":"additional","affiliation":[{"name":"Department of Animal Breeding and Husbandry, Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2754-0571","authenticated-orcid":false,"given":"Sharmin Aqter","family":"Rony","sequence":"additional","affiliation":[{"name":"Department of Animal Breeding and Husbandry, Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany"},{"name":"Department of Parasitology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst","family":"Tholen","sequence":"additional","affiliation":[{"name":"Department of Animal Breeding and Husbandry, Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Schellander","sequence":"additional","affiliation":[{"name":"Department of Animal Breeding and Husbandry, Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6732-5534","authenticated-orcid":false,"given":"Muhammad Jasim","family":"Uddin","sequence":"additional","affiliation":[{"name":"Department of Animal Breeding and Husbandry, Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany"},{"name":"Virology and Infections Preparedness Laboratory, School of Veterinary Medicine, Murdoch University, Murdoch, WA 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1017\/S175173111000008X","article-title":"High Physiological Demands in Intensively Raised Pigs: Impact on Health and Welfare","volume":"4","author":"Prunier","year":"2010","journal-title":"Anim. 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