Major and minor receptor group human rhinoviruses penetrate from endosomes by different mechanisms

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Human rhinoviruses (HRVs) utilize specific receptors for cell entry: intercellular adhesion molecule 1 for major group HRVs and the low-density lipoprotein receptor for minor group HRVs.
• While the cytoplasmic RNA transfer mechanism is known for minor group HRV2, the in vivo uncoating process for major group HRVs remains unclear.

Purpose of the Study:

• To comparatively analyze the cell entry mechanisms of HRV2 (minor group) and HRV14 (major group).
• To elucidate the in vivo uncoating mechanism of major group HRVs.

Main Methods:

• Comparative analysis of HRV2 and HRV14 cell entry using free-flow electrophoresis.
• Separation of viral particles from endosomal and plasma membrane fractions.
• Assessment of viral uncoating under varying conditions.

Main Results:

• Free-flow electrophoresis effectively separated free viral particles from those associated with endosomes and plasma membranes.
• HRV14 was primarily recovered from endosomes under conditions that inhibit uncoating.
• Under uncoating-promoting conditions, the proportion of free HRV14 particles increased, with viral elution correlating with membraneous material rather than distinct endosomal peaks.

Conclusions:

• The uncoating of HRV14 appears to involve the lysis of the endosomal membrane.
• This lysis leads to the release of subviral 135S and 80S particles into the cytoplasm.
• The findings provide insight into the distinct cell entry pathways of major group HRVs.