Abstract
There is a growing interest in unraveling gene expression mechanisms leading to viral host invasion and infection progression. Current findings reveal that long non-coding RNAs (lncRNAs) are implicated in the regulation of the immune system by influencing gene expression through a wide range of mechanisms. By mining whole-transcriptome shotgun sequencing (RNA-seq) data using machine learning approaches, we detected two lncRNAs (ENSG00000254680 and ENSG00000273149) that are downregulated in a wide range of viral infections and different cell types, including blood monocluclear cells, umbilical vein endothelial cells, and dermal fibroblasts. The efficiency of these two lncRNAs was positively validated in different viral phenotypic scenarios. These two lncRNAs showed a strong downregulation in virus-infected patients when compared to healthy control transcriptomes, indicating that these biomarkers are promising targets for infection diagnosis. To the best of our knowledge, this is the very first study using host lncRNAs biomarkers for the diagnosis of human viral infections.
Highlights
The majority of erroneous antibiotic prescriptions occur in virus-infected patients, for which antibiotics offer no benefit except for mixed viral/bacterial infections [1,2]
We evaluated if patients clustered according to their disease status when applying the Viral Score (VS; see methods) to different groups represented by several pathogens and tissues
It has been reported that a major problem in the study of long non-coding RNAs (lncRNAs) in animal models is the lack of evolutionary conservation of the lncRNAs between species, which constitutes a major barrier in extrapolating results from animal models to humans [30]
Summary
The majority of erroneous antibiotic prescriptions occur in virus-infected patients, for which antibiotics offer no benefit except for mixed viral/bacterial infections [1,2]. The development of a fast and accurate diagnostic testing to early distinguish viral from bacterial infections in clinical settings and hospitals would facilitate a reduction in the overuse of wide-spectrum antibiotics, helping physicians make the right decisions and fight the appearance of antibiotic-resistant bacteria. Obtaining results from cultures usually takes 48–72 h, a timeframe that might be inadequate for decision-making in terms of antibiotic prescriptions to children with suspected infection. Bacterial cultures have limited sensitivity, to the extent that, e.g., failure to detect causal microorganisms occurs in 50% of pneumonia patients in critical care units [4,5]. In a large international collaborative study, Martinón-Torres et al [7] recently reported that pathogen detection has been of limited help to distinguish viral from bacterial infection
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