title: The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles.
abstract: Arenaviruses cause severe diseases in humans but establish asymptomatic, lifelong infections in rodent reservoirs. Persistently-infected rodents harbor high levels of defective interfering (DI) particles, which are thought to be important for establishing persistence and mitigating virus-induced cytopathic effect. Little is known about what drives the production of DI particles. We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. In contrast, DI particle release critically requires the PPXY late domain and is ESCRT-dependent. Additionally, the terminal tyrosine in the PPXY motif is reversibly phosphorylated and our findings indicate that this posttranslational modification may regulate DI particle formation. Thus we have uncovered a new role for the PPXY late domain and a possible mechanism for its regulation.
authors.affiliation: Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, Vermont, United States of America.|Cellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Ziegler
authors.affiliation: Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Philip
authors.initials: P
authors.lastname: Eisenhauer
authors.affiliation: Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Bruce
authors.affiliation: Department of Biology, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Marion E
authors.initials: ME
authors.lastname: Weir
authors.affiliation: Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, Vermont, United States of America.|Cellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: King
authors.affiliation: Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, Vermont, United States of America.|Cellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Klaus
authors.affiliation: Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Dimitry N
authors.initials: DN
authors.lastname: Krementsov
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Shirley
authors.affiliation: Department of Biology, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Ballif
authors.affiliation: Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, Vermont, United States of America.|Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Botten
mesh_terms: D002460:Cell Line; D003673:Defective Viruses / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D014771:Virion / Q000378:metabolism*; D057074:Virus Release
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport