Gimap5 promoted RSV degradation through interaction with M6PR

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Respiratory syncytial virus (RSV) causes severe respiratory illness in infants.
• GTPases of the immune-associated protein family (GIMAP) are implicated in infection and stress responses.
• Gimap5 (GIMAP5) is a GIMAP family member potentially involved in anti-infectious immunity.

Purpose of the Study:

• To investigate the role of Gimap5 in RSV infection.
• To explore the therapeutic potential of targeting GIMAP5 against RSV.

Main Methods:

• RT-qPCR, Western blot, and immunofluorescence assays to assess gene and protein expression.
• Transmission electron microscopy to observe viral degradation.
• Computer virtual screening to identify GIMAP5-targeting compounds.
• In vitro and in vivo experiments to evaluate anti-RSV effects.

Main Results:

• RSV infection downregulated GIMAP5 and M6PR expression.
• GIMAP5 interacts with M6PR to enhance RSV degradation in lysosomes.
• GIMAP5 downregulates IGF1R, a major RSV receptor, inhibiting viral entry.
• Three small molecule GIMAP5 agonists effectively inhibited RSV infection and complications in vitro and in vivo.

Conclusions:

• GIMAP5 plays a crucial role in combating RSV by facilitating viral clearance and reducing viral entry.
• GIMAP5 agonists represent a promising therapeutic strategy for managing RSV infections and associated complications.