title: A self-perpetuating repressive state of a viral replication protein blocks superinfection by the same virus.
abstract: Diverse animal and plant viruses block the re-infection of host cells by the same or highly similar viruses through superinfection exclusion (SIE), a widely observed, yet poorly understood phenomenon. Here we demonstrate that SIE of turnip crinkle virus (TCV) is exclusively determined by p28, one of the two replication proteins encoded by this virus. p28 expressed from a TCV replicon exerts strong SIE to a different TCV replicon. Transiently expressed p28, delivered simultaneously with, or ahead of, a TCV replicon, largely recapitulates this repressive activity. Interestingly, p28-mediated SIE is dramatically enhanced by C-terminally fused epitope tags or fluorescent proteins, but weakened by N-terminal modifications, and it inversely correlates with the ability of p28 to complement the replication of a p28-defective TCV replicon. Strikingly, p28 in SIE-positive cells forms large, mobile punctate inclusions that trans-aggregate a non-coalescing, SIE-defective, yet replication-competent p28 mutant. These results support a model postulating that TCV SIE is caused by the formation of multimeric p28 complexes capable of intercepting fresh p28 monomers translated from superinfector genomes, thereby abolishing superinfector replication. This model could prove to be applicable to other RNA viruses, and offer novel targets for antiviral therapy.
authors.affiliation: Department of Plant Pathology, The Ohio State University, Wooster, Ohio, United States of America.|State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhang
authors.affiliation: Department of Plant Pathology, The Ohio State University, Wooster, Ohio, United States of America.
authors.forename: Rong
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Plant Pathology, The Ohio State University, Wooster, Ohio, United States of America.
authors.forename: Qin
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Plant Pathology, The Ohio State University, Wooster, Ohio, United States of America.
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Plant Pathology, The Ohio State University, Wooster, Ohio, United States of America.|Molecular and Cellular Imaging Center, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, Ohio, United States of America.
authors.forename: Tea
authors.identifier: 0000-0001-7412-0433
authors.initials: T
authors.lastname: Meulia
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
authors.forename: Randal
authors.identifier: 0000-0002-6592-1471
authors.initials: R
authors.lastname: Halfmann
authors.affiliation: State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Plant Pathology, The Ohio State University, Wooster, Ohio, United States of America.
authors.forename: Feng
authors.identifier: 0000-0003-0079-3496
authors.initials: F
authors.lastname: Qu
mesh_terms: D019184:Carmovirus / Q000502:physiology*; D015151:Immunoblotting; D018613:Microscopy, Confocal; D010935:Plant Diseases / Q000821:virology; D015163:Superinfection / Q000382:microbiology*; D014026:Nicotiana / Q000821:virology; D014779:Virus Replication / Q000502:physiology*