Filovirus Entry A Novelty in the Viral Fusion World.docVIP

Viruses 2012, 4, 258-275; doi:10.3390/v4020258 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Filovirus Entry: A Novelty in the Viral Fusion World Catherine L. Hunt, Nicholas J. Lennemann and Wendy Maury * Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA; E-Mails: catherine-l-miller@ (C.L.H); nicholas-lennemann@ (N.J.L) * Author to whom correspondence should be addressed; E-Mail: wendy-maury@; Tel.: +1-319-335-8021; Fax: +1-319-335-9006. Received: 23 December 2011; in revised form: 24 January 2012 / Accepted: 30 January 2012 / Published: 7 February 2012 Abstract: Ebolavirus (EBOV) and Marburgvirus (MARV) that compose the filovirus family of negative strand RNA viruses infect a broad range of mammalian cells. Recent studies indicate that cellular entry of this family of viruses requires a series of cellular protein interactions and molecular mechanisms, some of which are unique to filoviruses and others are commonly used by all viral glycoproteins. Details of this entry pathway are highlighted here. Virus entry into cells is initiated by the interaction of the viral glycoprotein1 subunit (GP1) with both adherence factors and one or more receptors on the surface of host cells. On epithelial cells, we recently demonstrated that TIM-1 serves as a receptor for this family of viruses, but the cell surface receptors in other cell types remain unidentified. Upon receptor binding, the virus is internalized into endosomes primarily via macropinocytosis, but perhaps by other mechanisms as well. Within the acidified endosome, the heavily glycosylated GP1 is cleaved to a smaller form by the low pH-dependent cellular proteases Cathepsin L and B, exposing residues in the receptor binding site (RBS). Details of the molecular events following cathepsin-dependent trimming of GP1 are currently incomplete; however,