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Journal of Virology, August 2007, p. 8648-8655, Vol. 81, No. 16
0022-538X/07/$08.00+0     doi:10.1128/JVI.01569-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Enterovirus 70 Receptor Utilization Is Controlled by Capsid Residues That Also Regulate Host Range and Cytopathogenicity{triangledown}

Melissa Stewart Kim and Vincent R. Racaniello*

Department of Microbiology, Columbia University College of Physicians & Surgeons, 701 W. 168th St., New York, New York 10032

Received 21 July 2006/ Accepted 17 May 2007

Enterovirus type 70, an etiologic agent of acute hemorrhagic conjunctivitis, may bind different cellular receptors depending on cell type. To understand how EV70-receptor interaction is controlled, we studied two variants of the virus with distinct receptor utilization. EV70-Rmk, derived by passage in rhesus monkey kidney cells, replicates poorly in HeLa cells and does not cause cytopathic effects. Decay accelerating factor (DAF) is not a cell receptor for EV70-Rmk. Passage of EV70-Rmk in HeLa cells lead to isolation of EV70-Dne, which does not replicate in rhesus monkey kidney cells but grows to high titers in HeLa cells and causes cytopathic effects. DAF is sufficient for cell entry of EV70-Dne. EV70-Rmk replicates in human eye and brain-derived cell lines, whereas the Dne strain replicates only in HeLa cells and in conjunctiva-derived 15C4 cells. The two EV70 strains differ by five amino acid changes in the viral capsid. Single substitution of four of the five EV70-Rmk amino acids with the residue from EV70-Dne leads to lytic replication in HeLa cells. Conversely, substitution of any of the five EV70-Dne amino acids with the EV70-Rmk amino acid does not alter replication in HeLa cells. Three of these capsid amino acids are predicted to be located in the canyon encircling the fivefold axis of symmetry, one amino acid is found at the fivefold axis of symmetry, and one is located the interior of the capsid. The five EV70 residues define a region of the capsid that controls viral host range, DAF utilization, and cytopathogenicity.

* Corresponding author. Mailing address: Department of Microbiology, Columbia University College of Physicians & Surgeons, 701 W. 168th St. New York, NY 10032. Phone: (212) 305-5707. Fax: (212) 305-5106. E-mail: vrr1{at}columbia.edu

{triangledown} Published ahead of print on 30 May 2007.

Journal of Virology, August 2007, p. 8648-8655, Vol. 81, No. 16
0022-538X/07/$08.00+0     doi:10.1128/JVI.01569-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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