Human Coronavirus 229E Infection Alters Histone Proteoforms

Area of Science:

• Virology
• Proteomics
• Epigenetics

Background:

• Viruses utilize host epigenetic mechanisms, including histone modifications, to manipulate host gene expression for replication.
• Understanding how viruses alter host epigenetics is crucial for deciphering viral pathogenesis.

Purpose of the Study:

• To investigate changes in histone proteoforms in lung fibroblast cells upon human coronavirus 229E (HCoV-229E) infection.
• To explore the role of histone truncation in viral-host interactions.

Main Methods:

• Top-down proteomics was used to quantify histone proteoforms in HCoV-229E-infected and mock-infected MRC-5 cells.
• Differential abundance analysis was performed to identify changes in histone proteoform levels and modifications.

Main Results:

• A total of 572 proteoforms were identified, with 461 assigned to core histones (H2A, H2B, H3, H4).
• 200 histone proteoforms were quantifiable, showing differential abundance in response to HCoV-229E infection.
• A significant decrease in truncated histone proteoforms, specifically C-terminally truncated H2A and N-terminally truncated H3, was observed in infected cells.

Conclusions:

• Top-down proteomics effectively resolves unique histone proteoform truncation states.
• HCoV-229E infection alters histone proteoform abundance and truncation patterns.
• These findings support the hypothesis that viruses modify histone length to influence host gene expression.