title: Cell-cell contact promotes Ebola virus GP-mediated infection.
abstract: Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Here we provide evidence that cell-cell contact promotes infection mediated by the glycoprotein (GP) of EBOV. Interestingly, expression of EBOV GP alone, even in the absence of retroviral Gag-Pol, is sufficient to transfer a retroviral vector encoding Tet-off from cell to cell. Cell-to-cell infection mediated by EBOV GP is blocked by inhibitors of actin polymerization, but appears to be less sensitive to KZ52 neutralization. Treatment of co-cultured cells with cathepsin B/L inhibitors, or an entry inhibitor 3.47 that targets the receptor NPC1 for virus binding, also blocks cell-to-cell infection. Cell-cell contact also enhances spread of rVSV bearing GP in monocytes and macrophages, the primary targets of natural EBOV infection. Altogether, our study reveals that cell-cell contact promotes EBOV GP-mediated infection, and provides new insight into understanding EBOV spread and viral pathogenesis.
authors.affiliation: Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Miao
authors.affiliation: Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Minghua
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zheng
authors.affiliation: Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Fredric S
authors.initials: FS
authors.lastname: Cohen
authors.affiliation: Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA. Electronic address: liushan@missouri.edu.
authors.forename: Shan-Lu
authors.initials: SL
authors.lastname: Liu
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D029043:Ebolavirus / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D000077296:Niemann-Pick C1 Protein; D011991:Receptors, Virus / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus
keywords: Cell-to-cell infection; Ebola virus; GP