Vesicle-associated membrane protein 5 is an intrinsic defense factor for embryonic stem cells against coronaviruses

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Embryonic stem cells (ESCs) exhibit significant resistance to viral infections, independent of interferon signaling.
• The molecular mechanisms underlying this intrinsic antiviral state in ESCs are not fully understood.

Purpose of the Study:

• To identify the specific factors and mechanisms responsible for the antiviral resistance observed in ESCs.
• To investigate the role of identified factors against a broad range of viral pathogens, including coronaviruses.

Main Methods:

• Expression analysis of VAMP5 in ESCs and mesodermal cells.
• In vitro assays to assess the antiviral activity of VAMP5 against SARS-CoV-2 and other coronaviruses.
• Co-immunoprecipitation and microscopy to determine the interaction of VAMP5 with viral proteins and its localization within infected cells.

Main Results:

• Vesicle-associated membrane protein 5 (VAMP5) was identified as a potent antiviral factor highly expressed in ESCs and mesoderm.
• VAMP5 effectively restricts the replication of SARS-CoV-2, its variants, and other pathogenic coronaviruses, as well as viruses from different families.
• VAMP5 localizes to double-membrane vesicles (DMVs) and inhibits viral RNA synthesis by interacting with viral non-structural protein 8 (NSP8).

Conclusions:

• VAMP5 acts as a cell-autonomous antiviral defense mechanism in ESCs by disrupting DMV integrity and interfering with viral RNA replication complexes.
• VAMP5 represents a promising target for developing novel, broad-spectrum antiviral therapies against diverse viral infections.