title: FAM134B, the Selective Autophagy Receptor for Endoplasmic Reticulum Turnover, Inhibits Replication of Ebola Virus Strains Makona and Mayinga.
abstract: Selective autophagy of the endoplasmic reticulum (termed ER-phagy) is controlled by members of the FAM134 reticulon protein family. Here we used mouse embryonic fibroblasts from mice deficient in FAM134B to examine the role of the ER in replication of historic (Mayinga) or contemporary (Makona GCO7) strains of Ebola virus (EBOV). Loss of FAM134B resulted in 1-2 log10higher production of infectious EBOV, which was associated with increased production of viral proteins GP and VP40 and greater accumulation of nucleocaspid lattices. In addition, only 10% of wild-type cells contained detectable nucleoprotein, whereas knockout of FAM134B resulted in 80% of cells positive for nucleoprotein. Together, these data suggest that FAM134B-dependent ER-phagy is an important limiting event in EBOV replication in mouse cells and may have implications for further development of antiviral therapeutics and murine models of infection.
authors: Laboratory of Virology.
authors: Abhilash I
authors: AI
authors: Chiramel
authors: Laboratory of Virology.
authors: Jonathan D
authors: JD
authors: Dougherty
authors: Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana.
authors: Vinod
authors: V
authors: Nair
authors: Laboratory of Virology.
authors: Shelly J
authors: SJ
authors: Robertson
authors: Laboratory of Virology.
authors: Sonja M
authors: SM
authors: Best
mesh_terms: D000818:Animals; D001343:Autophagy; D002478:Cells, Cultured; D029043:Ebolavirus / Q000235:genetics / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D055786:Gene Knockout Techniques; D019142:Hemorrhagic Fever, Ebola / Q000821:virology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009698:Nucleoproteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: C545052:Fam134b protein, mouse; D008565:Membrane Proteins; D009698:Nucleoproteins
keywords: ER-phagy; Ebolavirus; FAM134B; mouse models; reticulon; selective autophagy; virus replication