Transcriptomics-inferred dynamics of SARS-CoV-2 interactions with host epithelial cells

Area of Science:

• Virology
• Molecular Biology
• Cellular Biology

Background:

• Virus-host interactions are crucial for understanding infection dynamics and identifying therapeutic targets.
• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection profoundly impacts host cell processes.

Purpose of the Study:

• To investigate the dynamic interplay between SARS-CoV-2 replication and the host cell's transcriptional response.
• To identify host pathways that can be targeted for antiviral therapy.

Main Methods:

• Time-resolved RNA sequencing of SARS-CoV-2 infected Caco-2 cells.
• Mathematical modeling of virus replication and host-virus interactions.
• Assessment of host-targeted kinase inhibitors against viral replication.

Main Results:

• SARS-CoV-2 infection rapidly alters host gene expression, affecting inflammatory, ribosomal, and mitochondrial pathways.
• Viral proteins were found to inhibit the host antiviral response, with viral transcripts exceeding host translation capacity.
• Targeting specific kinase-dependent pathways in host cells proved effective in inhibiting viral replication.

Conclusions:

• The study delineates a temporal sequence of SARS-CoV-2 host-virus interactions.
• Host cell pathways, particularly kinase-dependent ones, represent viable targets for developing novel antiviral strategies against SARS-CoV-2.