Red Blood Cell-Derived Small Extracellular Vesicles Inhibit Influenza Virus through Surface-Displayed Sialic Acids

Area of Science:

• Virology
• Nanotechnology
• Biochemistry

Background:

• Influenza A virus (IAV) attachment to host cells relies on hemagglutinin (HA) binding to sialic acids (SAs).
• Disrupting HA-SA interactions is a key antiviral strategy, independent of viral mutations or drug resistance.

Purpose of the Study:

• To investigate the potential of red blood cell-derived small extracellular vesicles (RBC sEVs) as nanodecoys against IAV.
• To evaluate the role of surface-displayed SAs on RBC sEVs in inhibiting IAV infection.

Main Methods:

• RBC sEVs were utilized for their natural abundance of surface-displayed SAs.
• Multivalent HA-SA interactions between IAV and RBC sEVs were analyzed.
• The anti-IAV efficacy of RBC sEVs was assessed in a dose-dependent manner.
• The impact of enzymatic SA removal from RBC sEVs on their antiviral activity was determined.

Main Results:

• RBC sEVs effectively inhibited IAV attachment and infection through high-avidity multivalent HA-SA binding.
• The antiviral efficacy of RBC sEVs demonstrated a clear dose-dependent relationship.
• Enzymatic removal of SAs from RBC sEVs significantly reduced their anti-IAV properties.

Conclusions:

• RBC sEVs possess intrinsic anti-IAV properties mediated by their native surface SAs.
• RBC sEVs show significant potential as a novel antiviral therapeutic strategy against influenza A virus.