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Pathway of rhinovirus disruption by soluble intercellular adhesion molecule 1 (ICAM-1): an intermediate in which
1Center for Blood Research, Boston, Massachusetts 02115.
Abstract:
We have examined the pathway of rhinovirus interaction with soluble intercellular adhesion molecule 1 (sICAM-1). Binding of sICAM-1 to rhinovirus serotypes 3 and 14 gives particles with sedimentation coefficients from 145 to 120S, depending on the amount of sICAM-1 bound. The formation of 120S particles is faster and more extensive at a neutral pH than at an acidic pH. A large number of receptors (> 30) can bind to human rhinovirus 3 without disruption. Disruption by sICAM-1 of rhinovirus that yields 80S particles is strongly temperature dependent and is antagonized by a low pH. Interestingly, sICAM-1 remains bound to the viral capsid after RNA is released, although in smaller amounts than those observed for the native virus. We have found heterogeneity both between and within 80S particle preparations in the VP4 content and number of bound receptors. The ability of the virus to remain bound to its receptor during the uncoating process may facilitate the transport of the viral genome into the cytoplasm in vivo.
Insights
Soluble intercellular adhesion molecule 1 (sICAM-1) binding affects rhinovirus structure and stability. The virus remains attached to sICAM-1 even after RNA release, potentially aiding genome delivery into host cells.
Area of Science:
- Virology
- Molecular Biology
- Biochemistry
Background:
- Rhinoviruses are major causes of human respiratory illness.
- Intercellular adhesion molecule 1 (ICAM-1) is a primary cellular receptor for many rhinovirus serotypes.
- Understanding rhinovirus-receptor interactions is crucial for developing antiviral strategies.
Purpose of the Study:
- To investigate the structural changes and stability of rhinovirus upon binding with soluble ICAM-1 (sICAM-1).
- To elucidate the role of pH and temperature in rhinovirus-sICAM-1 complex formation and dissociation.
- To examine the fate of sICAM-1 and viral components during rhinovirus uncoating.
Main Methods:
- Sedimentation analysis to determine particle coefficients.
- pH and temperature dependency studies.
- Analysis of viral capsid and RNA integrity post-interaction.
Main Results:
- sICAM-1 binding induced structural changes in rhinovirus serotypes 3 and 14, forming 145S to 120S particles.
- 120S particle formation was favored at neutral pH and higher temperatures.
- Disruption into 80S particles was temperature-dependent and pH-antagonized.
- sICAM-1 remained bound to the viral capsid after RNA release, with heterogeneity in VP4 content and receptor binding within 80S particles.
Conclusions:
- sICAM-1 binding significantly alters rhinovirus structure and stability.
- The interaction is sensitive to environmental factors like pH and temperature.
- The sustained binding of sICAM-1 to the capsid post-uncoating may be a mechanism for efficient viral genome delivery into the cytoplasm.