Exocyst complex component 2 is a potential host factor for SARS-CoV-2 infection.

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• The global epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates understanding host-pathogen interactions.
• Research has primarily focused on viral receptors and proteases, leaving other host factors under-explored.

Purpose of the Study:

• To identify and characterize host factors crucial for SARS-CoV-2 infection.
• To investigate the role of exocyst complex component 2 (EXOC2) in SARS-CoV-2 pathogenesis.

Main Methods:

• Utilized induced pluripotent stem cells (iPS cells) and airway organoids (AO) for infection studies.
• Employed CRISPR screening and RNA-sequencing data to identify host factors.
• Performed EXOC2 knockdown experiments and measured viral nucleocapsid (N) expression and virus copy number.
• Conducted immunostaining and analyzed Interferon Omega 1 (IFNW1) expression.

Main Results:

• Exocyst complex component 2 (EXOC2) was identified as a significant host factor for SARS-CoV-2.
• EXOC2 knockdown drastically reduced intracellular SARS-CoV-2 nucleocapsid (N) expression (to 3.7%) and extracellular virus copy number (to 1.6%).
• EXOC2 knockdown was shown to downregulate SARS-CoV-2 infection, partly by regulating IFNW1 expression.

Conclusions:

• EXOC2 plays a critical role in supporting SARS-CoV-2 infection.
• Modulating EXOC2 expression presents a potential therapeutic strategy for controlling SARS-CoV-2.
• Further research into EXOC2's function in viral infection is warranted.