Exogenous Coronavirus Interacts With Endogenous Retrotransposon in Human Cells

Area of Science:

• Molecular Biology
• Virology
• Genetics

Background:

• Coronaviruses, including MERS-CoV, SARS-CoV, and SARS-CoV-2, cause significant respiratory and organ damage globally.
• The precise impact of coronavirus infection on host cellular mechanisms remains largely unknown.
• Retrotransposons are mobile genetic elements whose dysregulation is linked to various diseases.

Purpose of the Study:

• To investigate the effect of MERS-CoV, SARS-CoV, and SARS-CoV-2 infection on host cell transcriptomes.
• To explore the relationship between coronavirus infection and retrotransposon activity.
• To understand potential implications for disease severity and diagnostic strategies.

Main Methods:

• Transcriptome analysis of human lung cells infected with MERS-CoV, SARS-CoV, and SARS-CoV-2.
• Analysis of SARS-CoV-2 infected human intestinal organoids.
• Investigation of retrotransposon expression, TET gene upregulation, and chimeric RNA formation.

Main Results:

• All three coronaviruses induced increased retrotransposon expression and TET gene upregulation in infected lung cells.
• Retrotransposon upregulation was also observed in SARS-CoV-2 infected intestinal organoids.
• Evidence suggests long-term epigenetic inheritance of retrotransposon upregulation and the formation of chimeric transcripts between retrotransposons and viral RNA.

Conclusions:

• Coronavirus infection dysregulates host retrotransposon expression, potentially increasing genome instability and disease severity, especially in individuals with pre-existing conditions like cancer or in the elderly.
• The formation of chimeric transcripts suggests a potential mechanism for viral genome integration into the host.
• Diagnostic primer and probe design should consider targeting the middle of the viral genome for improved detection of live viruses.