title: Positive and negative effects of adenovirus type 5 helper functions on adeno-associated virus type 5 (AAV5) protein accumulation govern AAV5 virus production.
abstract: Full replication of adeno-associated virus type 5 (AAV5) is sustained by adenovirus type 5 (Ad5) helper functions E1a, E1b, E2a, E4Orf6, and virus-associated (VA) RNA; however, their combined net enhancement of AAV5 replication was comprised of both positive and negative individual effects. Although Ad5 E4Orf6 was required for AAV5 genomic DNA replication, it also functioned together with E1b to degrade de novo-expressed, preassembled AAV5 capsid proteins and Rep52 in a proteosome-dependent manner. VA RNA enhanced accumulation of AAV5 protein, overcoming the degradative effects of E4Orf6, and was thus required to restore adequate amounts of AAV5 proteins necessary to achieve efficient virus production.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, 1201 E. Rollins Road, Columbia, MO 65211-7310, USA.
authors.forename: Ramnath
authors.initials: R
authors.lastname: Nayak
authors.forename: David J
authors.initials: DJ
authors.lastname: Pintel
mesh_terms: D017456:Adenovirus Early Proteins / Q000235:genetics / Q000378:metabolism; D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology*; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D000229:Dependovirus / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D005814:Genes, Viral; D006378:Helper Viruses / Q000235:genetics / Q000502:physiology*; D006801:Humans; D012367:RNA, Viral / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
chemical_list: D017456:Adenovirus Early Proteins; D036022:Capsid Proteins; D004279:DNA, Viral; D012367:RNA, Viral; D014764:Viral Proteins