Journal
VIRUS RESEARCH
Volume 230, Issue -, Pages 29-37Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.virusres.2017.01.001
Keywords
Respiratory syncytial virus; Viral persistence; Transcriptome; Microarray; NLRP3 inflammasome; Conditioned medium
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Funding
- Consejo Nacional de Ciencia y Tecnologia, Mexico [179838]
- Direction General de Asuntos del Personal Academic, Universidad Nacional Autonoma de Mexico [PAPIIT IN218916]
- Faculty of Medicine, UNAM
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Cells susceptible to persistent viral infections undergo important changes in their biological functions as a consequence of the expression of viral gene products that are capable of altering the gene expression profile of the host cell. Previously, we reported that persistence of the RSV genome in a mouse macrophage cell line induces important alterations in cell homeostasis, including constitutive expression of IFN-13 and other pro-inflammatory cytokines. Here, we postulated that changes in the homeostasis of non-infected macrophages could be induced by soluble factors secreted by persistently RSV- infected macrophages. To test this hypothesis, non-infected mouse macrophages were treated with conditioned medium (CM) collected from cultures of persistently RSV- infected macrophages. Total RNA was extracted and a microarray-based gene expression analysis was performed. Non-infected macrophages, treated under similar conditions with CM obtained from cultures of non-infected macrophages, were used as a control to establish differential gene expression between the two conditions. Results showed that CM from the persistently RSV-infected cultures altered expression of a total of 95 genes in non-infected macrophages, resulting in an antiviral gene-transcription profile along with inhibition of the inflammatory response, since some inflammatory genes were down-regulated, including Nlrp3 and 11-1 beta, both related to the inflammasome pathway. However, down-regulation of NIrp3 and 11-1 beta was reversible upon acute RSV infection. Additionally, we observed that the inflammatory response, evaluated by secreted IL-1 3, a final product of the inflammasome activity, was enhanced during acute RSV infection in macrophages treated with CM from persistently RSV-infected cultures, compared to that in macrophages treated with the control CM. This suggests that soluble factors secreted during RSV persistence may induce an exacerbated inflammatory response in non-infected cells. (C) 2017 Elsevier B.V. All rights reserved.
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