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Published on: September 20, 2024
Transcriptome-based analysis of human peripheral blood reveals regulators of immune response in different viral
Sergey M Ivanov1,2, Olga A Tarasova1, Vladimir V Poroikov1
1Department of Bioinformatics, Institute of Biomedical Chemistry, Moscow, Russia.
Introduction:
There are difficulties in creating direct antiviral drugs for all viruses, including new, suddenly arising infections, such as COVID-19. Therefore, pathogenesis-directed therapy is often necessary to treat severe viral infections and comorbidities associated with them. Despite significant differences in the etiopathogenesis of viral diseases, in general, they are associated with significant dysfunction of the immune system. Study of common mechanisms of immune dysfunction caused by different viral infections can help develop novel therapeutic strategies to combat infections and associated comorbidities.
Methods:
To identify common mechanisms of immune functions disruption during infection by nine different viruses (cytomegalovirus, Ebstein-Barr virus, human T-cell leukemia virus type 1, Hepatitis B and C viruses, human immunodeficiency virus, Dengue virus, SARS-CoV, and SARS-CoV-2), we analyzed the corresponding transcription profiles from peripheral blood mononuclear cells (PBMC) using the originally developed pipeline that include transcriptome data collection, processing, normalization, analysis and search for master regulators of several viral infections. The ten datasets containing transcription data from patients infected by nine viruses and healthy people were obtained from Gene Expression Omnibus. The analysis of the data was performed by Genome Enhancer pipeline.
Results:
We revealed common pathways, cellular processes, and master regulators for studied viral infections. We found that all nine viral infections cause immune activation, exhaustion, cell proliferation disruption, and increased susceptibility to apoptosis. Using network analysis, we identified PBMC receptors, representing proteins at the top of signaling pathways that may be responsible for the observed transcriptional changes and maintain the current functional state of cells.
Discussion:
The identified relationships between some of them and virus-induced alteration of immune functions are new and have not been found earlier, e.g., receptors for autocrine motility factor, insulin, prolactin, angiotensin II, and immunoglobulin epsilon. Modulation of the identified receptors can be investigated as one of therapeutic strategies for the treatment of severe viral infections.
Insights
Developing new antiviral drugs is challenging. This study reveals common immune system disruptions across nine viral infections, identifying key receptors for potential new therapies against severe viral diseases.
Area of Science:
- Immunology
- Virology
- Computational Biology
Background:
- Developing direct antiviral drugs for emerging viruses like COVID-19 is difficult.
- Pathogenesis-directed therapy is crucial for severe viral infections and associated conditions.
- Viral infections often lead to significant immune system dysfunction.
Purpose of the Study:
- To identify common mechanisms of immune dysfunction across nine different viral infections.
- To find master regulators responsible for immune alterations in viral infections.
- To explore novel therapeutic strategies targeting shared immune pathways.
Main Methods:
- Analyzed transcriptome profiles from peripheral blood mononuclear cells (PBMC) of patients with nine viral infections.
- Utilized a custom pipeline for data collection, processing, normalization, and analysis.
- Employed network analysis to identify key receptors and signaling pathways involved in immune disruption.
Main Results:
- All nine viral infections induced immune activation, exhaustion, disrupted cell proliferation, and increased apoptosis.
- Identified common pathways and master regulators across diverse viral infections.
- Discovered novel PBMC receptors (e.g., for insulin, prolactin) linked to virus-induced immune changes.
Conclusions:
- Shared immune dysregulation mechanisms exist across various viral infections.
- Specific PBMC receptors represent potential therapeutic targets for severe viral diseases.
- Modulating identified receptors offers a promising strategy for treating viral infections and comorbidities.
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