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Porcine reproductive and respiratory syndrome virus induces IL-1? production depending on TLR4/MyD88 pathway and NLRP3 inflammasome in primary porcine alveolar macrophages.

ABSTRACT: Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide since the late 1980s. Previous studies have reported that PRRSV infection induced the production of IL-1 ? . However, the cellular sensors and signaling pathways involved in this process have not been elucidated yet. Here, we studied the mechanisms responsible for the production of IL-1 ? in response to highly pathogenic PRRSV. Upon PRRSV infection of primary porcine alveolar macrophages, both mRNA expression and secretion of IL-1 ? were significantly increased in a time- and dose-dependent manner. We also investigated the role of several pattern-recognition receptors and adaptor molecules in this response and showed that the TLR4/MyD88 pathway and its downstream signaling molecules, NF- ? B, ERK1/2, and p38 MAPKs, were involved in IL-1 ? production during PRRSV infection. Treatment with specific inhibitors or siRNA knockdown assays demonstrated that components of the NLRP3 inflammasome were crucial for IL-1 ? secretion but not for IL-1 ? mRNA expression. Furthermore, TLR4/MyD88/NF- ? B signaling pathway was involved in PRRSV-induced expression of NLRP3 inflammasome components. Together, our results deciphered the pathways leading from recognition of PRRSV to the production and release of IL-1 ? , providing a deeper knowledge of the mechanisms of PRRSV-induced inflammation responses.

SUBMITTER: Bi J

PROVIDER: S-EPMC4055429 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Porcine reproductive and respiratory syndrome virus induces IL-1β production depending on TLR4/MyD88 pathway and NLRP3 inflammasome in primary porcine alveolar macrophages.

Bi Jing J Song Shuang S Fang Liurong L Wang Dang D Jing Huiyuan H Gao Li L Cai Yidong Y Luo Rui R Chen Huanchun H Xiao Shaobo S

Mediators of inflammation 20140521

Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide since the late 1980s. Previous studies have reported that PRRSV infection induced the production of IL-1 β . However, the cellular sensors and signaling pathways involved in this process have not been elucidated yet. Here, we studied the mechanisms responsible for the production of IL-1 β in response to highly pathogenic PRRSV. Upon PRRSV infection of primary porci ...[more]

PMID: 24966466

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Project description:Porcine reproductive and respiratory syndrome (PRRS) has devastated pig industries worldwide for many years. It is caused by a small RNA virus (PRRSV), which targets almost exclusively pig monocytes or macrophages. In the present study, five SAGE (serial analysis of gene expression) libraries derived from 0 hour mock-infected and 6, 12, 16 and 24 hours PRRSV-infected porcine alveolar macrophages (PAMs) produced a total 643,255 sequenced tags with 91,807 unique tags. Differentially expressed (DE) tags were then detected using the Bayesian framework followed by gene/mRNA assignment, arbitrary selection and manual annotation, which determined 699 DE genes for reactome analysis. The DAVID, KEGG and REACTOME databases assigned 573 of the DE genes into six biological systems, 60 functional categories and 504 pathways. The six systems are: cellular processes, genetic information processing, environmental information processing, metabolism, organismal systems and human diseases as defined by KEGG with modification. Self-organizing map (SOM) analysis further grouped these 699 DE genes into ten clusters, reflecting their expression trends along these five time points. Based on the number one functional category in each system, cell growth and death, transcription processes, signal transductions, energy metabolism, immune system and infectious diseases formed the major reactomes of PAMs responding to PRRSV infection. Our investigation also focused on dominant pathways that had at least 20 DE genes identified, multi-pathway genes that were involved in 10 or more pathways and exclusively-expressed genes that were included in one system. Overall, our present study reported a large set of DE genes, compiled a comprehensive coverage of pathways, and revealed system-based reactomes of PAMs infected with PRRSV. We believe that our reactome data provides new insight into molecular mechanisms involved in host genetic complexity of antiviral activities against PRRSV and lays a strong foundation for vaccine development to control PRRS incidence in pigs.

Dataset Information

Porcine reproductive and respiratory syndrome virus induces IL-1? production depending on TLR4/MyD88 pathway and NLRP3 inflammasome in primary porcine alveolar macrophages.

Publications

Porcine reproductive and respiratory syndrome virus induces IL-1β production depending on TLR4/MyD88 pathway and NLRP3 inflammasome in primary porcine alveolar macrophages.

Similar Datasets

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