title: Ebola virus mediated infectivity is restricted in canine and feline cells.
abstract: Ebolaviruses and marburgviruses belong to the Filoviridae family and often cause severe, fatal hemorrhagic fever in humans and non-human primates. The magnitude of the 2014 outbreak in West Africa and the unprecedented emergence of Ebola virus disease (EVD) in the United States underscore the urgency to better understand the dynamics of Ebola virus infection, transmission and spread. To date, the susceptibility and possible role of domestic animals and pets in the transmission cycle and spread of EVD remains unclear. We utilized infectious VSV recombinants and lentivirus pseudotypes expressing the EBOV surface glycoprotein (GP) to assess the permissiveness of canine and feline cells to EBOV GP-mediated entry. We observed a general restriction in EBOV-mediated infection of primary canine and feline cells. To address the entry mechanism, we used cells deficient in NPC1, a host protein implicated in EBOV entry, and a pharmacological blockade of cholesterol transport, to show that an NPC1-dependent mechanism of EBOV entry is conserved in canine and feline cells. These data demonstrate that cells of canine and feline origin are susceptible to EBOV GP mediated infection; however, infectivity of these cells is reduced significantly compared to controls. Moreover, these data provide new insights into the mechanism of EBOV GP mediated entry into cells of canine and feline origin.
authors.affiliation: Departments of Pathobiology and Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Bart
authors.affiliation: Departments of Pathobiology and Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Gordon
authors.initials: G
authors.lastname: Ruthel
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Nathan H
authors.initials: NH
authors.lastname: Vande Burgt
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Haines
authors.affiliation: Departments of Pathobiology and Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Susan W
authors.initials: SW
authors.lastname: Volk
authors.affiliation: Departments of Pathobiology and Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Vite
authors.affiliation: Departments of Pathobiology and Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Freedman
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Bates
authors.affiliation: Departments of Pathobiology and Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: rharty@vet.upenn.edu.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Harty
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002415:Cats; D002478:Cells, Cultured; D004285:Dogs; D029043:Ebolavirus / Q000145:classification / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D013045:Species Specificity; D014760:Viral Fusion Proteins; D053586:Virus Internalization
chemical_list: D002352:Carrier Proteins; D014760:Viral Fusion Proteins
keywords: Canine; Ebola virus; Entry; Feline; Filovirus; Infectivity; Pseudotypes; Susceptibility; VSV recombinant