title: Adeno-associated viruses undergo substantial evolution in primates during natural infections.
abstract: Adeno-associated viruses (AAVs) are single-stranded DNA viruses that are endemic in human populations without known clinical sequelae and are being evaluated as vectors for human gene therapy. To better understand the biology of this virus, we examined a number of nonhuman primate species for the presence of previously uncharacterized AAVs and characterized their structure and distribution. AAV genomes were widely disseminated throughout multiple tissues of a variety of nonhuman primate species. Surprising diversity of sequence, primarily localized to hypervariable regions of the capsid protein, was detected. This diversity of sequence is caused, in part, by homologous recombination of co-infecting parental viruses that modify the serologic reactivity and tropism of the virus. This is an example of rapid molecular evolution of a DNA virus in a way that was formerly thought to be restricted to RNA viruses.
authors.affiliation: Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
authors.forename: Guangping
authors.initials: G
authors.lastname: Gao
authors.forename: Mauricio R
authors.initials: MR
authors.lastname: Alvira
authors.forename: Suryanarayan
authors.initials: S
authors.lastname: Somanathan
authors.forename: You
authors.initials: Y
authors.lastname: Lu
authors.forename: Luk H
authors.initials: LH
authors.lastname: Vandenberghe
authors.forename: John J
authors.initials: JJ
authors.lastname: Rux
authors.forename: Roberto
authors.initials: R
authors.lastname: Calcedo
authors.forename: Julio
authors.initials: J
authors.lastname: Sanmiguel
authors.forename: Zahra
authors.initials: Z
authors.lastname: Abbas
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: D000818:Animals; D016477:Artifacts; D001483:Base Sequence; D017931:DNA Primers; D000229:Dependovirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D016679:Genome, Viral; D005843:Geography; D008251:Macaca; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D010215:Papio; D010322:Parvoviridae Infections / Q000662:veterinary*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D018419:Primate Diseases / Q000821:virology*; D015203:Reproducibility of Results
chemical_list: D017931:DNA Primers