SARS-CoV-2 productively infects human gut enterocytes

Area of Science:

• Virology
• Gastroenterology
• Cell Biology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, primarily affecting the lungs via respiratory transmission.
• Clinical observations suggest the intestine may also be a target organ for SARS-CoV-2.
• The angiotensin-converting enzyme 2 (ACE2) receptor, crucial for viral entry, is highly expressed on intestinal cells.

Purpose of the Study:

• To investigate the susceptibility of the intestinal epithelium to SARS-CoV-2 infection.
• To determine if the intestine can support viral replication.
• To establish human small intestinal organoids (hSIOs) as a model for studying coronavirus infection.

Main Methods:

• Infection of human small intestinal organoids (hSIOs) with SARS-CoV and SARS-CoV-2.
• Confocal and electron microscopy to visualize viral presence and replication within enterocytes.
• Messenger RNA (mRNA) expression analysis to assess the host response to viral infection.

Main Results:

• Enterocytes within hSIOs were readily infected by both SARS-CoV and SARS-CoV-2.
• Infectious viral particles were produced by infected enterocytes.
• mRNA analysis revealed the induction of a generic viral response program in hSIOs.

Conclusions:

• The intestinal epithelium is capable of supporting SARS-CoV-2 replication.
• hSIOs provide a viable experimental model for studying the biology and infection mechanisms of coronaviruses.
• These findings highlight the gastrointestinal tract as a significant site for SARS-CoV-2 activity.