Identifying signatures of host genome-wide transcriptional patterns can be a tool for biomarker discovery as well as for understanding molecular mechanisms and pathophysiological signatures of disease states.
In this study by Loke et al., transcriptional profiling analysis of pediatric patients from Nicaragua with a predominantly DENV-1 infection was performed, and the gene signatures between healthy, dengue fever (DF), dengue haemorrhaigic fever (DHF) and dengue shock syndrome (DSS) were compared. Enrolment criteria consisted of hospitalised patients younger than 15 years of age. Whole blood was collected during acute illness (days 3-6).
Unsupervised clustering reveal that DHF and DF patients cluster distinctly from the DSS patients. Interestingly, many of the genes that separate these two groups are involved in ‘protein biosynthesis’ and ‘protein metabolism and modification’. A large number of mitochondrial ribosomal proteins and ‘nucleic acid binding’ were also flagged (See Figure above).
Genes related to metabolism, oxidative phosphorylation, protein targeting, nucleic acid metabolism, purine and pyrimidine metabolism, electron transport, DNA metabolism and replication, and protein metabolism and modification were differentially regulated by DF, DHF and DSS patients, reflecting a shared signature of DENV-1 infection.
On the other hand, the biological processes differentially expressed by DSS patients were protein metabolism and modification, intracellular protein traffic, pre-mRNA processing, mRNA splicing, nuclear transport, protein-lipid modification and protein folding.
Of note, the changes in metabolism genes cannot be seen in vitro. Instead, interferon signatures were upregulated.
Data is deposited in Gene Expression Omnibus (GEO) under GSE25226.