Receptor priming of major group human rhinoviruses for uncoating and entry at mild low-pH environments

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Receptor priming for low-pH-triggered entry was known for enveloped viruses.
• The entry mechanism of nonenveloped viruses, like major group human rhinoviruses (HRV), was less understood.
• Intercellular adhesion molecule-1 (ICAM-1) is a known receptor for major group HRV.

Purpose of the Study:

• To investigate if nonenveloped viruses, specifically major group HRV, employ receptor priming for cell entry.
• To elucidate the role of low pH and receptor interactions in HRV uncoating and infection.
• To determine if HRV entry follows the novel cell entry principle observed in enveloped viruses.

Main Methods:

• In vitro experiments assessing HRV uncoating at varying pH levels.
• Cell infection assays using agents that affect endosomal acidification (lysosomotropic agents).
• Testing the effect of nocodazole on HRV infection.
• Exposure of internalized HRV to mild low pH to overcome entry inhibition.

Main Results:

• Receptor priming by ICAM-1 primed HRV for efficient uncoating at mild low pH (5.5-6.0).
• Inhibition of endosomal acidification reduced or blocked HRV infection.
• The inhibitory effect of lysosomotropic agents could be reversed by exposing internalized HRV to mild low pH.
• Nocodazole did not affect HRV infection across tested serotypes.

Conclusions:

• Major group HRV utilize receptor priming for entry, similar to enveloped viruses.
• Receptor-primed HRV uncoating at low pH is essential for efficient cell membrane penetration.
• This mechanism likely occurs in vivo, involving receptor-mediated genome release during endosomal acidification.