Biodistribution and Cellular Internalization of Inactivated SARS-CoV-2 in Wild-Type Mice.

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Human angiotensin-converting enzyme 2 (ACE2) is the primary SARS-CoV-2 receptor, but wild-type rodents are resistant due to ACE2 variations.
• SARS-CoV-2 spike protein's heparin-binding motif (PRRAR) suggests interaction with rodent heparan sulfate proteoglycans (HSPGs).

Purpose of the Study:

• To investigate SARS-CoV-2 particle uptake in murine models via non-ACE2 pathways.
• To explore the role of syndecans, a type of HSPG, in SARS-CoV-2 internalization.

Main Methods:

• In vitro studies using murine cell lines expressing syndecan-4.
• In vivo studies involving intravenous administration of inactivated SARS-CoV-2 particles in mice.
• Analysis of viral particle distribution and tissue TNF-α levels.

Main Results:

• Inactivated SARS-CoV-2 particles were efficiently internalized by murine cell lines expressing syndecan-4.
• In vivo, inactivated SARS-CoV-2 was detected in multiple organs, including the brain.
• Uptake of inactivated SARS-CoV-2 led to increased TNF-α levels, particularly in the heart, indicating inflammation.

Conclusions:

• Rodent HSPGs, specifically syndecans, can mediate SARS-CoV-2 internalization, offering an alternative entry route.
• These findings expand the understanding of SARS-CoV-2 molecular interactions and potential host-pathogen dynamics beyond ACE2.
• The study highlights potential inflammatory responses associated with SARS-CoV-2 internalization in various tissues.