Gene expression in tonsils in swine following infection with porcine reproductive and respiratory syndrome virus

Authors: DONG, QIAN - Iowa State University; Lunney, Joan; LIM, KYU-SANG - Iowa State University; NGUYEN, YET - Iowa State University; HESS, ANDREW - Iowa State University; BEIKI, HAMID - Iowa State University; ROWLAND, RRR - Kansas State University; Walker, Kristen; REECY, J - Iowa State University; TUGGLE, CK - Iowa State University; DEKKERS, JCM - Iowa State University

Submitted to: BioMed Central (BMC) Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/2/2021
Publication Date: 2/22/2021
Citation: Dong, Q., Lunney, J.K., Lim, K., Nguyen, Y., Hess, A.S., Beiki, H., Rowland, R., Walker, K.E., Reecy, J., Tuggle, C., Dekkers, J. 2021. Gene expression in tonsils in swine following infection with porcine reproductive and respiratory syndrome virus. BioMed Central (BMC) Veterinary Research. 17:88. https://doi.org/10.1186/s12917-021-02785-1.
DOI: https://doi.org/10.1186/s12917-021-02785-1

Interpretive Summary: Porcine Reproductive and Respiratory Syndrome (PRRS) is a major disease of swine worldwide both from an economic and animal welfare standpoint. Unfortunately it can be a persistent infection with tonsils as a main site of persistence. A means of preventing, or identifying, pigs with persistent infection are desperately needed. Pigs with high tonsil virus levels, or the favorable PRRS resistance allele, had stronger tonsil inflammatory and cell-mediated immune response as measured by our extensive gene expression studies. These studies provide insights into potential mechanisms of PRRS viral persistence in tonsils which could be targeted to improve strategies to reduce or prevent PRRS viral rebreaks.

Technical Abstract: Background: 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 days post infection (dpi) were generated by RNA-seq and NanoString on 51 pigs that were selected to contrast the two PRRSV isolates, NVSL and KS06, high and low tonsil viral level at 42 dpi, and the AB (favorable) and AA (unfavorable) genotypes at a genetic marker (WUR) for the putative PRRSV resistance gene GBP5. Results: The number of differentially expressed genes (DEGs) differed markedly between models with and without accounting for cell-type enrichments (CE) in the samples, as predicted from RNA-seq data by the xCell software. 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 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 NVSL may be better than KS06 at evading host immune response and persist 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. The WUR genotype was associated with different effects on immune response in tonsils of pigs during the persistence stage, dependent on viral isolate and tonsil viral level. Conclusions: Results of this study provide insights into the effects of PRRSV isolate, TVclass, and WUR genotype on host immune response and into the potential mechanisms of PRRSV persistence in tonsils that could be targeted to improve strategies to reduce rebreaks.