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Journal of Virology, November 2003, p. 11985-11991, Vol. 77, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.22.11985-11991.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Receptor Priming of Major Group Human Rhinoviruses for Uncoating and Entry at Mild Low-pH Environments

Karolinska Institute, Department of Biosciences at NOVUM, Center for Biotechnology, 141 57 Huddinge, Sweden,¹ Centro Nacional de Biotecnología, Campus Universidad Autonoma, 28049 Madrid, Spain²

Received 9 May 2003/ Accepted 12 August 2003

Receptor priming of low-pH-triggered virus entry has been described for an enveloped virus (15). Here we show with major group human rhinoviruses (HRV) and its intercellular adhesion molecule-1 receptor that nonenveloped viruses follow this novel cell entry principle. In vitro the receptor primed HRV for efficient uncoating at mild low pH (5.5 to 6.0). Agents preventing endosomal acidification reduced or blocked rhinovirus cell infection, while nocodazole had no effect on infection of any serotype tested. The entry inhibitory effect of lysosomotropic agents was overcome by exposing cell-internalized HRV to mild low pH (5.5 to 6.0). We therefore conclude that receptor priming of major group HRV must occur in vivo as well. Cooperation of a cellular receptor and low pH in virus uncoating will polarize the exit of the genome to the receptor-bound, membrane-proximal region of the virus particle during acidification of endosomes. This process must be required for efficient penetration of the cellular membrane by viruses.

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