title: Adenovirus assembly is impaired by BMI1-related histone deacetylase activity.
abstract: Polycomb ring finger oncogene BMI1 (B cell-specific Moloney murine leukemia virus integration site 1) plays a critical role in development of several types of cancers. Here, we report an inverse relationship between levels of BMI1 expression and adenovirus (Ad) progeny production. Enforced BMI1 expression in A549 cells impaired Ad progeny production. In contrast, knocking-down of endogenous BMI1 expression enhanced progeny production of a conditionally replicating Ad and wild-type Ad5 and Ad11p. Ad vectors overexpressing BMI1 were not impaired in the replication of progeny genomes and in the expression of E1A and Ad structural proteins. However, 293 cells infected by Ad vector overexpressing BMI1 contained a large proportion of morphologically irregular Ad particles. This effect was reversed in 293 cells pre-treated with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) in parallel with the production of infectious Ad particles. Our findings suggest an inhibitory role of BMI1 in Ad morphogenesis that can be implied in Ad tropism and Ad-mediated cancer therapy.
authors.affiliation: The Rausing Laboratory, Department of Neurosurgery, Lund University, Lund, Sweden. Electronic address: manli.na@med.lu.se.
authors.forename: Manli
authors.initials: M
authors.lastname: Na
authors.affiliation: The Rausing Laboratory, Department of Neurosurgery, Lund University, Lund, Sweden. Electronic address: dongfeng.chen@med.lu.se.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Chen
authors.affiliation: ImaGene-iT AB, Medicon Village, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Holmqvist
authors.affiliation: Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ran
authors.affiliation: Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Pediatrics, Lund University, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Rebetz
authors.affiliation: The Rausing Laboratory, Department of Neurosurgery, Lund University, Lund, Sweden; Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Fan
mesh_terms: D000256:Adenoviridae / Q000276:immunology* / Q000502:physiology*; D002460:Cell Line; D006655:Histone Deacetylases / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D056189:Viral Tropism; D019065:Virus Assembly
chemical_list: C069077:BMI1 protein, human; D063150:Polycomb Repressive Complex 1; D006655:Histone Deacetylases
keywords: Adenovirus; Assembly; BMI1; Histone deacetylase; Polycomb