title: AAV2 X increases AAV6 rep/cap-driven rAAV production.
abstract: We have recently identified a new gene, involved in DNA replication, at the far 3' end of the adeno-associated virus type 2 (AAV2) genome. The AAV type 6 (AAV6) genome has a disrupted X open reading frame (ORF) whose two halves, when combined, have full-length homology and comparable size to AAV2 X. Hypothesizing that AAV6 X is inactive, we assessed if AAV2 X augments recombinant (r)AAV2 DNA replication and virion production, but with rep and cap trans-functions of AAV6. Using AAV2 X expressing HEK293 cell lines we show AAV2 X significantly boosts rAAV DNA replication/virion production, driven by AAV6 rep/cap as it does the AAV2 rep/cap system. Protein BLAST search for homology between AAV2 X and various AAV Rep78 proteins suggests that X might be AAV8 Rep78-derived and have some of its activities. These data suggest that AAV2 X, and the corresponding X genes of other AAV types/clades, warrant further study.
authors.affiliation: Central Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock,AR 72205, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Internal Medicine, Texas Tech University, Lubbock, TX 79408, USA.
authors.forename: M
authors.initials: M
authors.lastname: Chiriva-Internati
authors.affiliation: Central Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock,AR 72205, USA; Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, 4301 West Markham St., Little Rock, AR 72205, USA. Electronic address: Paul.Hermonat@va.gov.
authors.forename: P L
authors.initials: PL
authors.lastname: Hermonat
mesh_terms: D002460:Cell Line; D019295:Computational Biology; D004261:DNA Replication; D000229:Dependovirus / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D004847:Epithelial Cells / Q000821:virology; D019143:Evolution, Molecular; D006801:Humans; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism*; D017385:Sequence Homology; D014771:Virion / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D012324:RNA-Dependent RNA Polymerase
keywords: Adeno-associated virus type 2; Adeno-associated virus type 6; Adeno-associated virus type 8; DNA replication; Gene therapy; Rep78 protein; Rolling circle replication; Virion production; X gene; X protein
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