Transcriptomic profiling in childhood H1N1/09 influenza reveals reduced expression of protein synthesis genes

Jethro A Herberg, Myrsini Kaforou, Stuart Gormley, Edward R Sumner, Sanjay Patel, Kelsey D J Jones, Stéphane Paulus, Colin Fink, Federico Martinon-Torres, Giovanni Montana, Victoria J Wright, Michael Levin, Jethro A Herberg, Myrsini Kaforou, Stuart Gormley, Edward R Sumner, Sanjay Patel, Kelsey D J Jones, Stéphane Paulus, Colin Fink, Federico Martinon-Torres, Giovanni Montana, Victoria J Wright, Michael Levin

Abstract

We compared the blood RNA transcriptome of children hospitalized with influenza A H1N1/09, respiratory syncytial virus (RSV) or bacterial infection, and healthy controls. Compared to controls, H1N1/09 patients showed increased expression of inflammatory pathway genes and reduced expression of adaptive immune pathway genes. This was validated on an independent cohort. The most significant function distinguishing H1N1/09 patients from controls was protein synthesis, with reduced gene expression. Reduced expression of protein synthesis genes also characterized the H1N1/09 expression profile compared to children with RSV and bacterial infection, suggesting that this is a key component of the pathophysiological response in children hospitalized with H1N1/09 infection.

Keywords: Peptide Chain Initiation; RSV; eIF-2 Kinase; gene expression profiling; influenza; microarray analysis; pediatric; respiratory tract infection.

Figures

Figure 1.
Figure 1.
Unsupervised clustering of the top SDE transcripts for (A) H1N1/09 and controls (B) H1N1/09 and RSV and (C) H1N1/09 and bacterial infection. Heatmaps show separation of H1N1/09 and comparator groups by unsupervised Manhattan clustering, based on top SDE transcripts. Each row represents one transcript; each column represents one patient, with a red bar below indicating H1N1/09 and a blue bar a control (A), RSV (B), or bacterial infection (C). Curtailed transcript lists of highly significant probes were used for clarity (P value thresholds of 10−5 (n = 90 transcripts), .002 (n = 97), and .001 (n = 156), respectively, for control, RSV, and bacterial comparisons). Expression intensity is indicated by color (increased abundance in red, decreased in blue, intermediate in yellow).
Figure 2.
Figure 2.
Top canonical pathways differing between H1N1/09 and controls, RSV and bacterial infection. Each bar is colored in proportion to the number of SDE H1N1/09 transcripts increased (red) or decreased (green) in abundance relative to the comparator cohort. The total bar length is proportional to P value. Colored blocks next to each pathway are coded according to biological function. Protein synthesis pathways (yellow) were the most significant in all 3 comparisons, with predominant decreased expression in H1N1/09 patients relative to the comparator group. Innate immune pathway transcripts (brown) were increased in H1N1/09 patients, whereas adaptive immune transcripts (pink) were reduced relative to controls.

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