Comparative transcriptome analysis reveals key epigenetic targets in SARS-CoV-2 infection

Area of Science:

• Virology
• Epigenetics
• Molecular Biology

Background:

• Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a global health crisis.
• Understanding host cell responses, particularly transcriptional changes driven by epigenetic regulation, is crucial for developing therapeutics.
• While epigenetic changes are known in SARS-CoV and MERS-CoV infections, they are not fully characterized for SARS-CoV-2.

Purpose of the Study:

• To analyze transcriptomic data from cell lines and patient samples infected with SARS-CoV-2, SARS-CoV, and MERS-CoV.
• To identify key host cell genes, Transcription Factors, and Epifactors involved in the epigenetic response to these viral infections.
• To explore the therapeutic potential of targeting the epigenetic machinery for COVID-19 treatment.

Main Methods:

• Integrative analysis of multiple transcriptomes from infected cell lines and COVID-19 patient samples.
• Gene co-expression network analysis to identify modules of co-regulated genes.
• De-novo pathway enrichment analysis to identify relevant biological pathways and regulatory proteins.

Main Results:

• Characterization of distinct gene modules and protein pathways associated with SARS-CoV-2, SARS-CoV, and MERS-CoV infections.
• Identification of EP300, MOV10, RELA, and TRIM25 as key candidate proteins in the epigenetic response.
• Discovery of over 60 additional proteins implicated in the host epigenetic response to viral infection with therapeutic potential.

Conclusions:

• The study highlights the significant role of epigenetic regulation in host cell responses to SARS-CoV-2 infection.
• Targeting host cell epigenetic machinery presents a promising and feasible therapeutic strategy for treating COVID-19.
• Further research into these identified epigenetic factors could lead to novel antiviral drug development.