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ICAM-1 receptors and cold viruses
1School of Biological Sciences, University of Manchester, UK. jordi.bella@man.ac.uk
Abstract:
Human rhinoviruses (HRVs), the single most important etiologic agent of common colds, are small viruses composed of an icosahedral protein shell that encapsidates a single, positive RNA strand. Multiplication of HRVs occurs in the cytoplasm of the host cell. To produce infection, HRVs must first attach to specific cellular receptors embedded in the plasma membrane. Ninety percent of HRVs immunogenic variants use as receptor intercellular adhesion molecule-1 (ICAM-1), a cell surface glycoprotein that promotes intercellular signaling in processes derived from inflammation response. As HRV receptor, ICAM-1 positions the virus to within striking distance of the membrane, and then triggers a conformational change in the virus that ultimately results in delivery of the viral RNA genome into the cytoplasm, across a lipid bilayer. The interaction between ICAM-1 and HRVs has been analyzed by the combination of crystal structures of HRVs and ICAM-1 fragments with electron microscopy reconstructions of the complexes. The resulting molecular models are useful to address questions about receptor recognition, binding specificity, and mechanisms by which ICAM-1 induces virus uncoating.
Insights
Human rhinoviruses (HRVs), a leading cause of colds, use intercellular adhesion molecule-1 (ICAM-1) to infect cells. This interaction facilitates viral RNA delivery into the host cell cytoplasm for replication.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Human rhinoviruses (HRVs) are the primary cause of the common cold.
- HRVs are small viruses with an icosahedral protein shell containing a positive RNA strand.
- Viral replication occurs in the host cell cytoplasm.
Purpose of the Study:
- To investigate the molecular mechanisms of HRV infection.
- To understand the role of intercellular adhesion molecule-1 (ICAM-1) in HRV entry.
- To analyze receptor recognition and binding specificity between HRVs and ICAM-1.
Main Methods:
- Analysis of crystal structures of HRVs and ICAM-1 fragments.
- Electron microscopy reconstructions of HRV-ICAM-1 complexes.
- Development of molecular models to study virus-receptor interactions.
Main Results:
- Ninety percent of HRVs utilize ICAM-1 as their cellular receptor.
- ICAM-1 binding positions the virus for membrane penetration.
- ICAM-1 triggers conformational changes leading to viral RNA release into the cytoplasm.
Conclusions:
- ICAM-1 is crucial for HRV attachment and entry.
- Molecular models provide insights into HRV receptor recognition and uncoating mechanisms.
- Understanding this interaction can inform strategies against HRV infections.