The common cold in 3D

Modeling of the human rhinovirus C capsid suggests a novel topography with insights on receptor preference and immunogenicity

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Rhinoviruses (RV), the major causative agents of the common cold, fall into three species: A, B or C. The C species viruses eluded detection until 2006, despite causing up to half of infections in young children, because they do not propagate in common cell culture systems. Though there has been some success replicating them in primary donor samples and air-liquid-interface (ALI) cultures, these culture methods do not yield the amounts of virus needed to experimentally acquire a crystal structure.

We therefore used 3D protein modeling to construct a high-resolution model of the RV-C15 capsid, predicted accurate to about 2.6 angstroms. Combined with a robust sequence dataset, the model shows a drastic change in surface topography at the 5-fold axis compared to the RV-A and –B viruses, correlating with three large deletions in VP1 that are present in all characterized C-species viruses.

These dramatic changes in mass at the 5-fold axes are significant because this is often where the receptor binds. Previous work showed that the C-species uses a unique receptor to enter cells, and the absence of that receptor in common cell lines is the restricting factor to viral replication. The model can now be used to predict potential RV-C receptors.

Around the 5-fold axis is a canyon that contains a hydrophobic pocket, to which antiviral drugs are often targeted. In the RV-C species, however, this pocket is blocked by the presence of larger residues. No antiviral drug tested experimentally (in ALI cultures) was found to be effective on RV-C15, suggesting C-species-specific antivirals may need to be developed.


Introducing the authors
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About the research

Modeling of the human rhinovirus C capsid suggests a novel topography with insights on receptor preference and immunogenicity
Virology, Volume 448, 5 January 2014, Pages 176–184
Holly A. Basta, Jean-Yves Sgro, Ann C. Palmenberg

Read the full article on ScienceDirect.

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