Analysis of porcine bone marrow-derived macrophage cytokine responses to infection with PRRSV-1 strains of differing virulence
Porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) causes huge economic losses to the European pig industry. PRRSV-1 is divided into 3 subtypes and exhibits considerable antigenic heterogeneity. Due to its high mutation rate, PRRSV-1 is constantly evolving, and highly virulent, particul...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Virology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fviro.2022.980412/full |
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| author | Ben Jackson Tiphany Chrun Kay Childs Nanchaya Wanasen Jean-Pierre Frossard Simon P. Graham Julian Seago |
| author_facet | Ben Jackson Tiphany Chrun Kay Childs Nanchaya Wanasen Jean-Pierre Frossard Simon P. Graham Julian Seago |
| author_sort | Ben Jackson |
| collection | DOAJ |
| description | Porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) causes huge economic losses to the European pig industry. PRRSV-1 is divided into 3 subtypes and exhibits considerable antigenic heterogeneity. Due to its high mutation rate, PRRSV-1 is constantly evolving, and highly virulent, particularly subtype 3 strains, are continually emerging. The mechanism(s) underlying PRRSV-1 virulence have not been fully elucidated. In vivo studies have implicated replication kinetics, cell tropism and an enhanced pro-inflammatory cytokine response as potential contributing factors. However, few strains have been directly compared and differences in in vivo study design have hindered comparison, thus limiting our understanding of PRRSV-1 virulence. To address this knowledge gap, we sought to develop a reverse genetics and ex vivo model system, to attempt to identify correlates of PRRSV-1 virulence and attenuation in vitro. Herein we describe the use of primary porcine bone marrow-derived macrophages (BMDM) to investigate the growth kinetics and induced cytokine profiles of the highly virulent SU1-Bel strain, the low virulence 215-06 strain and the attenuated Olot/91 strain. We show that infection of BMDM with virulent PRRSV-1 strains induced higher expression of IL-6 and IL-8 and lower expression of TNF-α when compared with the attenuated strain. In addition, BMDM infected with SU1-Bel secreted significantly more IFN-α than those infected with PRRSV-1 strains of lower virulence. Interestingly, despite inducing less IFN-α than SU1-Bel, Olot/91 induced much higher levels of expression of several interferon-stimulated genes (ISGs), suggesting that Olot/91 may be less able to counteract type I IFN signaling which may contribute to its attenuated phenotype. |
| first_indexed | 2024-04-12T06:36:52Z |
| format | Article |
| id | doaj.art-5339b577f5e9477f9af9d9c2a2b425a8 |
| institution | Directory Open Access Journal |
| issn | 2673-818X |
| language | English |
| last_indexed | 2024-04-12T06:36:52Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Virology |
| spelling | doaj.art-5339b577f5e9477f9af9d9c2a2b425a82022-12-22T03:43:51ZengFrontiers Media S.A.Frontiers in Virology2673-818X2022-08-01210.3389/fviro.2022.980412980412Analysis of porcine bone marrow-derived macrophage cytokine responses to infection with PRRSV-1 strains of differing virulenceBen Jackson0Tiphany Chrun1Kay Childs2Nanchaya Wanasen3Jean-Pierre Frossard4Simon P. Graham5Julian Seago6The Pirbright Institute, Woking, United KingdomThe Pirbright Institute, Woking, United KingdomThe Pirbright Institute, Woking, United KingdomVirology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathumthani, ThailandAnimal and Plant Health Agency, Addlestone, United KingdomThe Pirbright Institute, Woking, United KingdomThe Pirbright Institute, Woking, United KingdomPorcine reproductive and respiratory syndrome virus 1 (PRRSV-1) causes huge economic losses to the European pig industry. PRRSV-1 is divided into 3 subtypes and exhibits considerable antigenic heterogeneity. Due to its high mutation rate, PRRSV-1 is constantly evolving, and highly virulent, particularly subtype 3 strains, are continually emerging. The mechanism(s) underlying PRRSV-1 virulence have not been fully elucidated. In vivo studies have implicated replication kinetics, cell tropism and an enhanced pro-inflammatory cytokine response as potential contributing factors. However, few strains have been directly compared and differences in in vivo study design have hindered comparison, thus limiting our understanding of PRRSV-1 virulence. To address this knowledge gap, we sought to develop a reverse genetics and ex vivo model system, to attempt to identify correlates of PRRSV-1 virulence and attenuation in vitro. Herein we describe the use of primary porcine bone marrow-derived macrophages (BMDM) to investigate the growth kinetics and induced cytokine profiles of the highly virulent SU1-Bel strain, the low virulence 215-06 strain and the attenuated Olot/91 strain. We show that infection of BMDM with virulent PRRSV-1 strains induced higher expression of IL-6 and IL-8 and lower expression of TNF-α when compared with the attenuated strain. In addition, BMDM infected with SU1-Bel secreted significantly more IFN-α than those infected with PRRSV-1 strains of lower virulence. Interestingly, despite inducing less IFN-α than SU1-Bel, Olot/91 induced much higher levels of expression of several interferon-stimulated genes (ISGs), suggesting that Olot/91 may be less able to counteract type I IFN signaling which may contribute to its attenuated phenotype.https://www.frontiersin.org/articles/10.3389/fviro.2022.980412/fullPRRSV-1SU1-Bel215-06Olot/91bone marrow-derived macrophagesproinflammatory cytokines |
| spellingShingle | Ben Jackson Tiphany Chrun Kay Childs Nanchaya Wanasen Jean-Pierre Frossard Simon P. Graham Julian Seago Analysis of porcine bone marrow-derived macrophage cytokine responses to infection with PRRSV-1 strains of differing virulence Frontiers in Virology PRRSV-1 SU1-Bel 215-06 Olot/91 bone marrow-derived macrophages proinflammatory cytokines |
| title | Analysis of porcine bone marrow-derived macrophage cytokine responses to infection with PRRSV-1 strains of differing virulence |
| title_full | Analysis of porcine bone marrow-derived macrophage cytokine responses to infection with PRRSV-1 strains of differing virulence |
| title_fullStr | Analysis of porcine bone marrow-derived macrophage cytokine responses to infection with PRRSV-1 strains of differing virulence |
| title_full_unstemmed | Analysis of porcine bone marrow-derived macrophage cytokine responses to infection with PRRSV-1 strains of differing virulence |
| title_short | Analysis of porcine bone marrow-derived macrophage cytokine responses to infection with PRRSV-1 strains of differing virulence |
| title_sort | analysis of porcine bone marrow derived macrophage cytokine responses to infection with prrsv 1 strains of differing virulence |
| topic | PRRSV-1 SU1-Bel 215-06 Olot/91 bone marrow-derived macrophages proinflammatory cytokines |
| url | https://www.frontiersin.org/articles/10.3389/fviro.2022.980412/full |
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