[HTML][HTML] Suppression of ribosomal protein synthesis and protein translation factors by Peg-interferon alpha/ribavirin in HCV patients blood mononuclear cells (PBMC)
R Gupta, S Kim, MW Taylor - Journal of Translational Medicine, 2012 - Springer
R Gupta, S Kim, MW Taylor
Journal of Translational Medicine, 2012•SpringerBackground We have previously reported the induction of many interferon stimulated genes
(ISGs) in PBMC collected from patients infected with HCV at various times after initiation of
interferon-ribavirin treatment using DNA microarrays to identify changes in gene expression
with time. Almost as many genes are down regulated (suppressed) during interferon-
ribavirin treatment as are up regulated. Methods DNA microarrays were analyzed by
different software, including MAS5 (Affymetrix-Kegg) and GSEA (gene set enrichment …
(ISGs) in PBMC collected from patients infected with HCV at various times after initiation of
interferon-ribavirin treatment using DNA microarrays to identify changes in gene expression
with time. Almost as many genes are down regulated (suppressed) during interferon-
ribavirin treatment as are up regulated. Methods DNA microarrays were analyzed by
different software, including MAS5 (Affymetrix-Kegg) and GSEA (gene set enrichment …
Background
We have previously reported the induction of many interferon stimulated genes (ISGs) in PBMC collected from patients infected with HCV at various times after initiation of interferon-ribavirin treatment using DNA microarrays to identify changes in gene expression with time. Almost as many genes are down regulated (suppressed) during interferon-ribavirin treatment as are up regulated.
Methods
DNA microarrays were analyzed by different software, including MAS5 (Affymetrix-Kegg) and GSEA (gene set enrichment analysis) to identify specific pathways both up regulated and down regulated. Data was assessed from a clinical trial, which was a microarray analysis from 68 patients.
Results
Up regulated genes included genes associated with NF-kb, toll like receptor cytokine -cytokine interaction, and complement and adhesion pathways. The most prominent pathway down regulated was that for ribosomal structural proteins, and eukaryotic translational factors. Down regulation of ribosomal protein genes continued through the treatment up to the last measurement, which was at day 28.
Conclusions
This suppression of the protein synthetic apparatus might explain the long-term side effects of interferon-ribavirin, and explain a non-specific effect of interferon-ribavirin on viral protein synthesis. There was no evidence for unique transcription factors or micro RNA involvement.
Springer