title: Rhinovirus uses a phosphatidylinositol 4-phosphate/cholesterol counter-current for the formation of replication compartments at the ER-Golgi interface.
abstract: Similar to other positive-strand RNA viruses, rhinovirus, the causative agent of the common cold, replicates on a web of cytoplasmic membranes, orchestrated by host proteins and lipids. The host pathways that facilitate the formation and function of the replication membranes and complexes are poorly understood. We show that rhinovirus replication depends on host factors driving phosphatidylinositol 4-phosphate (PI4P)-cholesterol counter-currents at viral replication membranes. Depending on the virus type, replication required phosphatidylinositol 4-kinase class 3beta (PI4K3b), cholesteryl-esterase hormone-sensitive lipase (HSL) or oxysterol-binding protein (OSBP)-like 1, 2, 5, 9, or 11 associated with lipid droplets, endosomes, or Golgi. Replication invariably required OSBP1, which shuttles cholesterol and PI4P between ER and Golgi at membrane contact sites. Infection also required ER-associated PI4P phosphatase Sac1 and phosphatidylinositol (PI) transfer protein beta (PITPb) shunting PI between ER-Golgi. These data support a PI4P-cholesterol counter-flux model for rhinovirus replication.
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland; Life Science Zurich Graduate School, Molecular Life Sciences Program, Zurich, Switzerland.
authors.forename: Pascal S
authors.initials: PS
authors.lastname: Roulin
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Mark
authors.initials: M
authors.lastname: Lötzerich
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors.forename: Federico
authors.initials: F
authors.lastname: Torta
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors.forename: Lukas B
authors.initials: LB
authors.lastname: Tanner
authors.affiliation: Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, University of Utrecht, 3584CL Utrecht, The Netherlands.
authors.forename: Frank J M
authors.initials: FJ
authors.lastname: van Kuppeveld
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address: urs.greber@imls.uzh.ch.
authors.forename: Urs F
authors.initials: UF
authors.lastname: Greber
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D012229:Rhinovirus / Q000201:enzymology* / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000378:metabolism; D014779:Virus Replication; D000098825:Oxysterol Binding Proteins
chemical_list: D018129:Phosphatidylinositol Phosphates; D011987:Receptors, Steroid; C496748:VAPB protein, human; D033921:Vesicular Transport Proteins; D000098825:Oxysterol Binding Proteins; C037178:phosphatidylinositol 4-phosphate; D002784:Cholesterol