{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:23:16Z","timestamp":1773296596477,"version":"3.50.1"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008370","name":"National Pork Board","doi-asserted-by":"publisher","award":["12-061"],"award-info":[{"award-number":["12-061"]}],"id":[{"id":"10.13039\/100008370","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008370","name":"National Pork Board","doi-asserted-by":"crossref","award":["14-223"],"award-info":[{"award-number":["14-223"]}],"id":[{"id":"10.13039\/100008370","id-type":"DOI","asserted-by":"crossref"}]},{"name":"USDA-NIFA","award":["2013-68004-20362"],"award-info":[{"award-number":["2013-68004-20362"]}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","award":["."],"award-info":[{"award-number":["."]}],"id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Vet Res"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Porcine reproductive and respiratory syndrome (PRRS) is a threat to pig production worldwide. Our objective was to understand mechanisms of persistence of PRRS virus (PRRSV) in tonsil. Transcriptome data from tonsil samples collected at 42\u2009days post infection (dpi) were generated by RNA-seq and NanoString on 51 pigs that were selected to contrast the two PRRSV isolates used, NVSL and KS06, high and low tonsil viral level at 42 dpi, and the favorable and unfavorable genotypes at a genetic marker (WUR) for the putative PRRSV resistance gene<jats:italic>GBP5<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The number of differentially expressed genes (DEGs) differed markedly between models with and without accounting for cell-type enrichments (CE) in the samples that were predicted from the RNA-seq data. This indicates that differences in cell composition in tissues that consist of multiple cell types, such as tonsil, can have a large impact on observed differences in gene expression. Based on both the NanoString and the RNA-seq data, KS06-infected pigs showed greater activation, or less inhibition, of immune response in tonsils at 42 dpi than NVSL-infected pigs, with and without accounting for CE. This suggests that the NVSL virus may be better than the KS06 virus at evading host immune response and persists in tonsils by weakening, or preventing, host immune responses. Pigs with high viral levels showed larger CE of immune cells than low viral level pigs, potentially to trigger stronger immune responses. Presence of high tonsil virus was associated with a stronger immune response, especially innate immune response through interferon signaling, but these differences were not significant when accounting for CE. Genotype at WUR was associated with different effects on immune response in tonsils of pigs during the persistence stage, depending on viral isolate and tonsil viral level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Results of this study provide insights into the effects of PRRSV isolate, tonsil viral level, and WUR genotype on host immune response and into potential mechanisms of PRRSV persistence in tonsils that could be targeted to improve strategies to reduce viral rebreaks. Finally, to understand transcriptome responses in tissues that consist of multiple cell types, it is important to consider differences in cell composition.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12917-021-02785-1","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T13:04:45Z","timestamp":1613999085000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Gene expression in tonsils in swine following infection with porcine reproductive and respiratory syndrome virus"],"prefix":"10.1186","volume":"17","author":[{"given":"Qian","family":"Dong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan K.","family":"Lunney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyu-Sang","family":"Lim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yet","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew S.","family":"Hess","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamid","family":"Beiki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond R. R.","family":"Rowland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M.","family":"Reecy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher K.","family":"Tuggle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1557-7577","authenticated-orcid":false,"given":"Jack C. M.","family":"Dekkers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"2785_CR1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.54846\/jshap\/754","volume":"21","author":"DJ Holtkamp","year":"2013","unstructured":"Holtkamp DJ, Kliebenstein JB, Neumann EJ, Zimmerman JJ, Rotto HF, Yoder TK. Assessment of the economic impact of porcine reproductive and respiratory syndrome virus on United States pork producers. J Swine Health Prod. 2013;21:72\u201384.","journal-title":"J Swine Health Prod"},{"key":"2785_CR2","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.prevetmed.2017.04.006","volume":"142","author":"H Nathues","year":"2017","unstructured":"Nathues H, Alarcon P, Rushton J, Jolie R, Fiebig K, Jimenez M, et al. Cost of porcine reproductive and respiratory syndrome virus at individual farm level \u2013 an economic disease model. Prev Vet Med. 2017;142:16\u201329.","journal-title":"Prev Vet Med"},{"key":"2785_CR3","doi-asserted-by":"crossref","unstructured":"Snijder EJ, Kikkert M, Fang Y. Arterivirus molecular biology and pathogenesis. J Gen Virol. 2013;94:2141\u201363.","DOI":"10.1099\/vir.0.056341-0"},{"key":"2785_CR4","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1089\/vim.2010.0051","volume":"23","author":"GJ Renukaradhya","year":"2010","unstructured":"Renukaradhya GJ, Alekseev K, Jung K, Fang Y, Saif LJ. Porcine reproductive and respiratory syndrome virus\u2013induced immunosuppression exacerbates the inflammatory response to porcine respiratory coronavirus in pigs. Viral Immunol. 2010;23:457\u201366.","journal-title":"Viral Immunol"},{"key":"2785_CR5","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1089\/jir.1998.18.485","volume":"18","author":"E Albina","year":"1998","unstructured":"Albina E, Carrat C, Charley B. Short communication: interferon-\u03b1 response to swine Arterivirus (PoAV), the porcine reproductive and respiratory syndrome virus. J Interf Cytokine Res. 1998;18:485\u201390.","journal-title":"J Interf Cytokine Res"},{"key":"2785_CR6","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1002\/jlb.56.4.507","volume":"56","author":"Y Zhou","year":"1994","unstructured":"Zhou Y, Lin G, Baarsch MJ, Scamurra RW, Murtaugh MP. Interleukin-4 suppresses inflammatory cytokine gene transcription in porcine macrophages. J Leukoc Biol. 1994;56:507\u201313.","journal-title":"J Leukoc Biol"},{"key":"2785_CR7","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1017\/S1466252307001387","volume":"9","author":"J Christopher-Hennings","year":"2008","unstructured":"Christopher-Hennings J, Nelson EA, Althouse GC, Lunney J. Comparative antiviral and proviral factors in semen and vaccines for preventing viral dissemination from the male reproductive tract and semen. Anim Health Res Rev. 2008;9:59\u201369.","journal-title":"Anim Health Res Rev"},{"key":"2785_CR8","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/S0378-1135(96)01337-5","volume":"55","author":"RW Wills","year":"1997","unstructured":"Wills RW, Zimmerman JJ, Yoon KJ, McGinley MJ, Hill HT, Platt KB. Porcine reproductive and respiratory syndrome virus: a persistent infection. Vet Microbiol. 1997;55:231\u201340.","journal-title":"Vet Microbiol"},{"key":"2785_CR9","doi-asserted-by":"publisher","first-page":"10834","DOI":"10.1128\/JVI.74.22.10834-10837.2000","volume":"74","author":"R Allende","year":"2000","unstructured":"Allende R, Laegreid WW, Kutish GF, Galeota JA, Wills RW, Osorio FA. Porcine reproductive and respiratory syndrome virus: description of persistence in individual pigs upon experimental infection. J Virol. 2000;74:10834\u20137.","journal-title":"J Virol"},{"key":"2785_CR10","doi-asserted-by":"publisher","first-page":"8700","DOI":"10.1128\/JVI.02551-09","volume":"84","author":"M Shi","year":"2010","unstructured":"Shi M, Lam TT-Y, Hon C-C, Murtaugh MP, Davies PR, Hui RK-H, et al. Phylogeny-based evolutionary, demographical, and geographical dissection of north American type 2 porcine reproductive and respiratory syndrome viruses. J Virol. 2010;84:8700\u201311.","journal-title":"J Virol"},{"key":"2785_CR11","doi-asserted-by":"crossref","unstructured":"Lunney JK, Steibel JP, Reecy JM, Fritz E, Rothschild MF, Kerrigan M. Probing genetic control of swine responses to PRRSV infection: current progress of the PRRS host genetics consortium. BMC Proc. 2011;5:1\u20135.","DOI":"10.1186\/1753-6561-5-S4-S30"},{"key":"2785_CR12","first-page":"16","volume":"95","author":"EH Waide","year":"2017","unstructured":"Waide EH, Tuggle CK, Ser\u00e3o NVL, Schroyen M, Hess A, Rowland RRR, et al. Genomewide association of piglet responses to infection with one of two porcine reproductive and respiratory syndrome virus isolates1. J Anim Sci. 2017;95:16\u201338.","journal-title":"J Anim Sci"},{"key":"2785_CR13","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1186\/s12864-015-1635-9","volume":"16","author":"JE Koltes","year":"2015","unstructured":"Koltes JE, Fritz-Waters E, Eisley CJ, Choi IS, Bao H, Kommadath A. Identification of a putative quantitative trait nucleotide in guanylate binding protein 5 for host response to PRRS virus infection. BMC Genomics. 2015;16:412.","journal-title":"BMC Genomics"},{"key":"2785_CR14","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.2527\/jas.2011-4464","volume":"90","author":"N Boddicker","year":"2012","unstructured":"Boddicker N, Waide EH, Rowland RRR, Lunney JK, Garrick DJ, Reecy JM. Evidence for a major QTL associated with host response to porcine reproductive and respiratory syndrome virus challenge. J Anim Sci. 2012;90:1733\u201346.","journal-title":"J Anim Sci"},{"key":"2785_CR15","unstructured":"Dunkelberger JR. The role of host genetics in susceptibility to viral disease in pigs. Grad Theses Diss. 2017;15297:71\u2013120."},{"key":"2785_CR16","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12711-016-0222-0","volume":"48","author":"AS Hess","year":"2016","unstructured":"Hess AS, Islam Z, Hess MK, Rowland RRR, Lunney JK, Doeschl-Wilson A, et al. Comparison of host genetic factors influencing pig response to infection with two north American isolates of porcine reproductive and respiratory syndrome virus. Genet Sel Evol. 2016;48:43.","journal-title":"Genet Sel Evol"},{"key":"2785_CR17","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.rvsc.2015.12.014","volume":"104","author":"G Abella","year":"2016","unstructured":"Abella G, Pena RN, Nogareda C, Armengol R, Vidal A, Moradell L. A WUR SNP is associated with European porcine reproductive and respiratory virus syndrome resistance and growth performance in pigs. Res Vet Sci. 2016;104:117\u201322.","journal-title":"Res Vet Sci"},{"key":"2785_CR18","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.virusres.2010.07.017","volume":"154","author":"L Darwich","year":"2010","unstructured":"Darwich L, Diaz I, Mateu E. Certainties, doubts and hypotheses in porcine reproductive and respiratory syndrome virus immunobiology. Virus Res. 2010;154:123\u201332.","journal-title":"Virus Res"},{"key":"2785_CR19","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.vetmic.2013.09.021","volume":"167","author":"E Weesendorp","year":"2013","unstructured":"Weesendorp E, Stockhofe-Zurwieden N, Popma-De Graaf DJ, Fijten H, Rebel JMJ. Phenotypic modulation and cytokine profiles of antigen presenting cells by European subtype 1 and 3 porcine reproductive and respiratory syndrome virus strains in vitro and in vivo. Vet Microbiol. 2013;167:638\u201350.","journal-title":"Vet Microbiol"},{"key":"2785_CR20","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.virol.2018.08.006","volume":"524","author":"R Guo","year":"2018","unstructured":"Guo R, Shang P, Carrillo CA, Sun Z, Lakshmanappa YS, Yan X, et al. Double-stranded viral RNA persists in vitro and in vivo during prolonged infection of porcine reproductive and respiratory syndrome virus. Virology. 2018;524:78\u201389.","journal-title":"Virology"},{"key":"2785_CR21","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1093\/jas\/sky446","volume":"97","author":"AS Hess","year":"2018","unstructured":"Hess AS, Lunney JK, Abrams S, Choi I, Trible BR, Hess MK, et al. Identification of factors associated with virus level in tonsils of pigs experimentally infected with porcine reproductive and respiratory syndrome virus 1. J Anim Sci. 2018;97:536\u201347.","journal-title":"J Anim Sci"},{"key":"2785_CR22","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1089\/vim.2009.0087","volume":"23","author":"JK Lunney","year":"2010","unstructured":"Lunney JK, Fritz ER, Reecy JM, Kuhar D, Prucnal E, Molina R, et al. Interleukin-8, interleukin-1\u03b2, and interferon-\u03b3 levels are linked to PRRS virus clearance. Viral Immunol. 2010;23:127\u201334.","journal-title":"Viral Immunol"},{"key":"2785_CR23","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1046\/j.1365-2567.1996.d01-705.x","volume":"89","author":"H Yang","year":"1996","unstructured":"Yang H, Parkhouse RME. Phenotypic classification of porcine lymphocyte subpopulations in blood and lymphoid tissues. Immunology. 1996;89:76\u201383.","journal-title":"Immunology"},{"key":"2785_CR24","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/S0165-2427(01)00335-X","volume":"82","author":"L Lamontagne","year":"2001","unstructured":"Lamontagne L, Page C, Larochelle R, Longtin D, Magar R. Polyclonal activation of B cells occurs in lymphoid organs from porcine reproductive and respiratory syndrome virus (PRRSV)-infected pigs. Vet Immunol Immunopathol. 2001;82:165\u201382.","journal-title":"Vet Immunol Immunopathol"},{"key":"2785_CR25","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/S0165-2427(99)00102-6","volume":"71","author":"K Kawashima","year":"1999","unstructured":"Kawashima K, Narita M, Yamada S. Changes in macrophage and lymphocyte subpopulations of lymphoid tissues from pigs infected with the porcine reproductive and respiratory syndrome virus (PRRSV). Vet Immunol Immunopathol. 1999;71:257\u201362.","journal-title":"Vet Immunol Immunopathol"},{"key":"2785_CR26","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1186\/s12864-019-5709-y","volume":"20","author":"HA Beiki","year":"2019","unstructured":"Beiki HA, Liu H, Huang J, Manchanda N, Nonneman D, Smith TPL, Reecy JMTC. Improved annotation of the domestic pig genome through integration of Iso-Seq and RNA-seq data. BMC Genomics. 2019;20:344.","journal-title":"BMC Genomics"},{"key":"2785_CR27","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/s13059-017-1349-1","volume":"18","author":"D Aran","year":"2017","unstructured":"Aran D, Hu Z, Butte AJ. xCell: digitally portraying the tissue cellular heterogeneity landscape. Genome Biol. 2017;18:220.","journal-title":"Genome Biol"},{"key":"2785_CR28","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1079\/AHRR200358","volume":"4","author":"DC Horter","year":"2003","unstructured":"Horter DC, Yoon K-J, Zimmerman JJ. A review of porcine tonsils in immunity and disease. Anim Health Res Rev. 2003;4:143\u201355.","journal-title":"Anim Health Res Rev"},{"key":"2785_CR29","doi-asserted-by":"publisher","first-page":"e97","DOI":"10.1093\/nar\/gkv412","volume":"43","author":"R Liu","year":"2015","unstructured":"Liu R, Holik AZ, Su S, Jansz N, Chen K, Leong HS, et al. Why weight? Modelling sample and observational level variability improves power in RNA-seq analyses. Nucleic Acids Res. 2015;43:e97.","journal-title":"Nucleic Acids Res"},{"key":"2785_CR30","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1038\/nmeth.2714","volume":"10","author":"T Steijger","year":"2013","unstructured":"Steijger T, Abril JF, Engstr\u00f6m PG, Kokocinski F, Consortium TR, Hubbard TJ, et al. Assessment of transcript reconstruction methods for RNA-seq. Nat Methods. 2013;10:1177\u201384.","journal-title":"Nat Methods"},{"key":"2785_CR31","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s10555-017-9677-x","volume":"36","author":"M Holinstat","year":"2017","unstructured":"Holinstat M. Normal platelet function. Cancer Metastasis Rev. 2017;36:195\u20138.","journal-title":"Cancer Metastasis Rev"},{"key":"2785_CR32","doi-asserted-by":"publisher","first-page":"4685","DOI":"10.4049\/jimmunol.1202672","volume":"190","author":"AA Aggrey","year":"2013","unstructured":"Aggrey AA, Srivastava K, Ture S, Field DJ, Morrell CN. Platelet induction of the acute-phase response is protective in murine experimental cerebral malaria. J Immunol. 2013;190:4685\u201391.","journal-title":"J Immunol"},{"key":"2785_CR33","doi-asserted-by":"publisher","first-page":"2759","DOI":"10.1182\/blood-2013-11-462432","volume":"123","author":"CN Morrell","year":"2014","unstructured":"Morrell CN, Aggrey AA, Chapman LM, Modjeski KL. Emerging roles for platelets as immune and inflammatory cells. Blood. 2014;123:2759\u201367.","journal-title":"Blood."},{"key":"2785_CR34","first-page":"2071","volume":"2017","author":"S Wetzel","year":"1864","unstructured":"Wetzel S, Seipold L, Saftig P. The metalloproteinase ADAM10: a useful therapeutic target? Biochim Biophys Acta Mol Cell Res. 1864;2017:2071\u201381.","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"2785_CR35","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1084\/jem.20091990","volume":"207","author":"DR Gibb","year":"2010","unstructured":"Gibb DR, El Shikh M, Kang D-J, Rowe WJ, El Sayed R, Cichy J, et al. ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo. J Exp Med. 2010;207:623\u201335.","journal-title":"J Exp Med"},{"key":"2785_CR36","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1093\/intimm\/dxn076","volume":"20","author":"L Tian","year":"2008","unstructured":"Tian L, Wu X, Chi C, Han M, Xu T, Zhuang Y. ADAM10 is essential for proteolytic activation of notch during thymocyte development. Int Immunol. 2008;20:1181\u20137.","journal-title":"Int Immunol"},{"key":"2785_CR37","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1111\/all.13261","volume":"73","author":"SR Damle","year":"2018","unstructured":"Damle SR, Martin RK, Cockburn CL, Lownik JC, Carlyon JA, Smith AD, et al. ADAM10 and Notch1 on murine dendritic cells control the development of type 2 immunity and IgE production. Allergy. 2018;73:125\u201336.","journal-title":"Allergy"},{"key":"2785_CR38","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s00251-011-0518-8","volume":"63","author":"T Ait-Ali","year":"2011","unstructured":"Ait-Ali T, Wilson AD, Carr\u00e9 W, Westcott DG, Frossard JP, Mellencamp MA, et al. Host inhibits replication of European porcine reproductive and respiratory syndrome virus in macrophages by altering differential regulation of type-I interferon transcriptional response. Immunogenetics. 2011;63:437\u201348.","journal-title":"Immunogenetics"},{"key":"2785_CR39","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/nature22366","volume":"545","author":"EL Huttlin","year":"2017","unstructured":"Huttlin EL, Bruckner RJ, Paulo JA, Cannon JR, Ting L, Baltier K, et al. Protein communities and disease networks. Nature. 2017;545:505\u20139.","journal-title":"Nature"},{"key":"2785_CR40","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1471-2164-11-22","volume":"11","author":"KM Rothgiesser","year":"2010","unstructured":"Rothgiesser KM, Fey M, Hottiger MO. Acetylation of p65 at lysine 314 is important for late NF- B-dependent gene expression. BMC Genomics. 2010;11:22.","journal-title":"BMC Genomics"},{"key":"2785_CR41","doi-asserted-by":"crossref","unstructured":"Richardson RM, Marjoram RJ, Barak LS, Snyderman R. Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J Immunol. 2003;170:2904\u201311.","DOI":"10.4049\/jimmunol.170.6.2904"},{"key":"2785_CR42","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1189\/jlb.0108001","volume":"83","author":"V Shpacovitch","year":"2008","unstructured":"Shpacovitch V, Feld M, Hollenberg MD, Luger TA, Steinhoff M. Role of protease-activated receptors in inflammatory responses, innate and adaptive immunity. J Leukoc Biol. 2008;83:1309\u201322.","journal-title":"J Leukoc Biol"},{"key":"2785_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1615\/CritRevImmunol.v24.i1.10","volume":"24","author":"MR Sarrias","year":"2004","unstructured":"Sarrias MR, Gronlund J, Padilla O, Madsen J, Holmskov U, Lozano F. The scavenger receptor cysteine-rich (SRCR) domain: an ancient and highly conserved protein module of the innate immune system. Crit Rev Immunol. 2004;24:1\u201338.","journal-title":"Crit Rev Immunol"},{"key":"2785_CR44","doi-asserted-by":"publisher","first-page":"2388","DOI":"10.1128\/MCB.00036-13","volume":"33","author":"O Busnadiego","year":"2013","unstructured":"Busnadiego O, Gonz\u00e1lez-Santamar\u00eda J, Lagares D, Guinea-Viniegra J, Pichol-Thievend C, Muller L, et al. LOXL4 is induced by transforming growth factor \u03b21 through Smad and JunB\/Fra2 and contributes to vascular matrix remodeling. Mol Cell Biol. 2013;33:2388\u2013401.","journal-title":"Mol Cell Biol"},{"key":"2785_CR45","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1038\/onc.2012.168","volume":"32","author":"A Bhandari","year":"2013","unstructured":"Bhandari A, Gordon W, Dizon D, Hopkin AS, Gordon E, Yu Z, et al. The Grainyhead transcription factor Grhl3\/Get1 suppresses miR-21 expression and tumorigenesis in skin: modulation of the miR-21 target MSH2 by RNA-binding protein DND1. Oncogene. 2013;32:1497\u2013507.","journal-title":"Oncogene"},{"key":"2785_CR46","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/ni.1828","volume":"11","author":"FJ Sheedy","year":"2010","unstructured":"Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O\u2019Leary JJ, Ruan Q, et al. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol. 2010;11:141\u20137.","journal-title":"Nat Immunol"},{"key":"2785_CR47","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.immuni.2007.11.020","volume":"28","author":"D Matza","year":"2008","unstructured":"Matza D, Badou A, Kobayashi KS, Goldsmith-Pestana K, Masuda Y, Komuro A, et al. A scaffold protein, AHNAK1, is required for calcium signaling during T cell activation. Immunity. 2008;28:64\u201374.","journal-title":"Immunity"},{"key":"2785_CR48","doi-asserted-by":"publisher","first-page":"4151","DOI":"10.1074\/jbc.M207789200","volume":"278","author":"SY Moon","year":"2003","unstructured":"Moon SY, Zang H, Zheng Y. Characterization of a brain-specific rho GTPase-activating protein, p200RhoGAP. J Biol Chem. 2003;278:4151\u20139.","journal-title":"J Biol Chem"},{"key":"2785_CR49","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.tcb.2005.01.002","volume":"15","author":"GM Bokoch","year":"2005","unstructured":"Bokoch GM. Regulation of innate immunity by rho GTPases. Trends Cell Biol. 2005;15:163\u201371.","journal-title":"Trends Cell Biol"},{"key":"2785_CR50","doi-asserted-by":"publisher","first-page":"e83567","DOI":"10.1371\/journal.pone.0083567","volume":"8","author":"ZU Islam","year":"2013","unstructured":"Islam ZU, Bishop SC, Savill NJ, Rowland RRR, Lunney JK, Trible B. Quantitative analysis of porcine reproductive and respiratory syndrome (PRRS) viremia profiles from experimental infection: a statistical modelling approach. PLoS One. 2013;8:e83567.","journal-title":"PLoS One"},{"key":"2785_CR51","volume-title":"FastQC: a quality control tool for high throughput sequence data","author":"S Andrews","year":"2010","unstructured":"Andrews S. FastQC: a quality control tool for high throughput sequence data. 2010. http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc."},{"key":"2785_CR52","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114\u201320.","journal-title":"Bioinformatics"},{"key":"2785_CR53","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15\u201321.","journal-title":"Bioinformatics"},{"key":"2785_CR54","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The sequence alignment\/map format and SAMtools. Bioinformatics. 2009;25:2078\u20139.","journal-title":"Bioinformatics."},{"key":"2785_CR55","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders S, Pyl PT, Huber W. HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31:166\u20139.","journal-title":"Bioinformatics"},{"key":"2785_CR56","volume-title":"Using NanoString transcriptomics to evaluate the fetal and placental response to congenital PRRSV infection","author":"JK Lunney","year":"2020","unstructured":"Lunney JK, Pasternak A, Malgarin C, Walker K, Ko H, Venner L, Linjun Hong L, Harding JC. Using NanoString transcriptomics to evaluate the fetal and placental response to congenital PRRSV infection. 2020. Manuscript in preparation."},{"key":"2785_CR57","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","volume":"9","author":"P Langfelder","year":"2008","unstructured":"Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559.","journal-title":"BMC Bioinformatics"},{"key":"2785_CR58","doi-asserted-by":"crossref","unstructured":"Law CW, Chen Y, Shi W, Smyth GK. Voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 2014;15:1\u201317.","DOI":"10.1186\/gb-2014-15-2-r29"},{"key":"2785_CR59","unstructured":"Nguyen Y. Multiple hypothesis testing and RNA-seq differential expression analysis accounting for dependence and relevant covariates. Grad Theses Diss. 2018;16426:33\u201361."},{"key":"2785_CR60","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1111\/1467-9868.00346","volume":"64","author":"JD Storey","year":"2002","unstructured":"Storey JD. A direct approach to false discovery rates. J R Stat Soc Ser B Stat Methodol. 2002;64:479\u201398.","journal-title":"J R Stat Soc Ser B Stat Methodol"},{"key":"2785_CR61","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1198\/108571106X129135","volume":"11","author":"D Nettleton","year":"2006","unstructured":"Nettleton D, Hwang JTG, Caldo RA, Wise RP. Estimating the number of true null hypotheses from a histogram of p values. J Agric Biol Environ Stat. 2006;11:337\u201356.","journal-title":"J Agric Biol Environ Stat"},{"key":"2785_CR62","doi-asserted-by":"crossref","unstructured":"Wang H, Horbinski C, Wu H, Liu Y, Sheng S, Liu J, et al. NanoStringDiff: a novel statistical method for differential expression analysis based on NanoString nCounter data. Nucleic Acids Res. 2016;44:e151.","DOI":"10.1093\/nar\/gkw677"},{"key":"2785_CR63","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","volume":"30","author":"A Kr\u00e4mer","year":"2014","unstructured":"Kr\u00e4mer A, Green J, Pollard J, Tugendreich S, Tugendreich S. Causal analysis approaches in ingenuity pathway analysis. Bioinformatics. 2014;30:523\u201330.","journal-title":"Bioinformatics"}],"container-title":["BMC Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-021-02785-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12917-021-02785-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-021-02785-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T17:07:04Z","timestamp":1724519224000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcvetres.biomedcentral.com\/articles\/10.1186\/s12917-021-02785-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,22]]},"references-count":63,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2785"],"URL":"https:\/\/doi.org\/10.1186\/s12917-021-02785-1","relation":{},"ISSN":["1746-6148"],"issn-type":[{"value":"1746-6148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,22]]},"assertion":[{"value":"8 November 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The Kansas State University Institutional Animal Care and Use Committee approved all experimental protocols for the animal trials used herein.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not Applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"88"}}