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Folate Receptor Alpha and Caveolae Are Not Required for Ebola Virus Glycoprotein-Mediated Viral Infection

Department of Microbiology,¹ Abramson Family Cancer Research Institute, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104-6076²

Received 28 March 2003/ Accepted 11 September 2003

Folate receptor alpha (FR) has been described as a factor involved in mediating Ebola virus entry into cells (6). Furthermore, it was suggested that interaction with FR results in internalization and subsequent viral ingress into the cytoplasm via caveolae (9). Descriptions of cellular receptors for Ebola virus and its entry mechanisms are of fundamental importance, particularly with the advent of vectors bearing Ebola virus glycoprotein (GP) being utilized for gene transfer into cell types such as airway epithelial cells. Thus, the ability of FR to mediate efficient entry of viral pseudotypes carrying GP was investigated. We identified cell lines and primary cell types such as macrophages that were readily infected by GP pseudotypes despite lacking detectable surface FR, indicating that this receptor is not essential for Ebola virus infection. Furthermore, we find that T-cell lines stably expressing FR are not infectible, suggesting that FR is also not sufficient to mediate entry. T-cell lines lack caveolae, the predominant route of FR-mediated folate metabolism. However, the coexpression of FR with caveolin-1, the major structural protein of caveolae, was not able to rescue infectivity in a T-cell line. In addition, other cell types lacking caveolae are fully infectible by GP pseudotypes. Finally, a panel of ligands to and soluble analogues of FR were unable to inhibit infection on a range of cell lines, questioning the role of FR as an important factor for Ebola virus entry.

* Mailing address for Paul Bates: Department of Microbiology, School of Medicine, University of Pennsylvania, 303A Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104-6076. Phone: (215) 573-3508. Fax: (215) 573-9069. E-mail: pbates{at}mail.med.upenn.edu.

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