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Productive entry pathways of human rhinoviruses
1Department of Pathophysiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Human rhinoviruses (HRVs) infect cells via endocytosis, where their capsids expand and release RNA. This process involves specific cellular receptors and mechanisms for viral RNA delivery into the cytoplasm.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Over 150 human rhinovirus (HRV) genome sequences are available.
- HRV species A and B utilize specific receptors (LDLR family or ICAM-1) for cell entry.
- HRV species C employs an unidentified receptor.
Purpose of the Study:
- To elucidate the entry and RNA release mechanisms of human rhinoviruses.
- To understand the structural changes in the HRV capsid during infection.
- To investigate the role of endocytosis in HRV replication.
Main Methods:
- Analysis of known HRV genome sequences.
- Studies on HRV-receptor interactions.
- Investigation of viral internalization and RNA release pathways in HeLa cells.
- Observation of capsid structural changes upon endosomal uptake.
Main Results:
- HRV-A and HRV-B depend on receptor-mediated endocytosis, primarily clathrin- and dynamin-dependent.
- Acidic endosomal compartments trigger HRV capsid expansion and pore formation.
- The viral protein VP4 is expelled, and VP1 N-termini are exposed, facilitating membrane attachment.
- Genomic RNA is released into the cytosol through capsid pores or via endosomal disruption.
Conclusions:
- HRVs utilize specific cellular receptors and endocytic pathways for entry.
- Significant capsid structural rearrangements are essential for viral RNA release.
- The released RNA enters the cytoplasm, initiating viral replication.
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