title: Phosphatidylserine vesicles enable efficient en bloc transmission of enteroviruses.
abstract: A central paradigm within virology is that each viral particle largely behaves as an independent infectious unit. Here, we demonstrate that clusters of enteroviral particles are packaged within phosphatidylserine (PS) lipid-enriched vesicles that are non-lytically released from cells and provide greater infection efficiency than free single viral particles. We show that vesicular PS lipids are co-factors to the relevant enterovirus receptors in mediating subsequent infectivity and transmission, in particular to primary human macrophages. We demonstrate that clustered packaging of viral particles within vesicles enables multiple viral RNA genomes to be collectively transferred into single cells. This study reveals a novel mode of viral transmission, where enteroviral genomes are transmitted from cell-to-cell en bloc in membrane-bound PS vesicles instead of as single independent genomes. This has implications for facilitating genetic cooperativity among viral quasispecies as well as enhancing viral replication.
authors: Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA; Federated Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
authors: Ying-Han
authors: YH
authors: Chen
authors: Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors: WenLi
authors: W
authors: Du
authors: Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors: Marne C
authors: MC
authors: Hagemeijer
authors: Federated Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
authors: Peter M
authors: PM
authors: Takvorian
authors: Federated Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
authors: Cyrilla
authors: C
authors: Pau
authors: Federated Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
authors: Ann
authors: A
authors: Cali
authors: Electron Microscopy Core Facility, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors: Christine A
authors: CA
authors: Brantner
authors: Electron Microscopy Core Facility, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors: Erin S
authors: ES
authors: Stempinski
authors: Electron Microscopy Core Facility, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors: Patricia S
authors: PS
authors: Connelly
authors: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA.
authors: Hsin-Chieh
authors: HC
authors: Ma
authors: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA.
authors: Ping
authors: P
authors: Jiang
authors: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA.
authors: Eckard
authors: E
authors: Wimmer
authors: Program in Computational Biology and Immunology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Grégoire
authors: G
authors: Altan-Bonnet
authors: Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA. Electronic address: nihal.altan-bonnet@nih.gov.
authors: Nihal
authors: N
authors: Altan-Bonnet
mesh_terms: D022162:Cytoplasmic Vesicles / Q000737:chemistry / Q000821:virology*; D004770:Enterovirus / Q000502:physiology*; D004769:Enterovirus Infections / Q000635:transmission*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000821:virology*; D010718:Phosphatidylserines; D017955:Poliovirus / Q000502:physiology; D012367:RNA, Viral / Q000378:metabolism; D012229:Rhinovirus / Q000502:physiology; D014779:Virus Replication
chemical_list: D010718:Phosphatidylserines; D012367:RNA, Viral