title: Differential requirements for clathrin endocytic pathway components in cellular entry by Ebola and Marburg glycoprotein pseudovirions.
abstract: Clathrin-mediated endocytosis was previously implicated as one of the cellular pathways involved in filoviral glycoprotein mediated viral entry into target cells. Here we have further dissected the requirements for different components of this pathway in Ebola versus Marburg virus glycoprotein (GP) mediated viral infection. Although a number of these components were involved in both cases; Ebola GP-dependent viral entry specifically required the cargo recognition proteins Eps15 and DAB2 as well as the clathrin adaptor protein AP-2. In contrast, Marburg GP-mediated infection was independent of these three proteins and instead required beta-arrestin 1 (ARRB1). These findings have revealed an unexpected difference between the clathrin pathway requirements for Ebola GP versus Marburg GP pseudovirion infection. Anthrax toxin also uses a clathrin-, and ARRB1-dependent pathway for cellular entry, indicating that the mechanism used by Marburg GP pseudovirions may be more generally important for pathogen entry.
authors.affiliation: Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Suchita
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hope
authors.forename: John A T
authors.initials: JA
authors.lastname: Young
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D019390:Arrestins / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism*; D029043:Ebolavirus / Q000502:physiology*; D004705:Endocytosis; D054884:Host-Pathogen Interactions; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D029024:Marburgvirus / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D014759:Viral Envelope Proteins / Q000378:metabolism*; D022701:Virosomes; D053586:Virus Internalization; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
chemical_list: C000605253:ARRB1 protein, human; D033962:Adaptor Protein Complex 2; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D019390:Arrestins; D002135:Calcium-Binding Proteins; D002966:Clathrin; C102885:DAB2 protein, human; C486206:EPS15 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D025521:Tumor Suppressor Proteins; D014759:Viral Envelope Proteins; D022701:Virosomes; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins