title: AAV-6 mediated efficient transduction of mouse lower airways.
abstract: AAV1 and AAV6 are two closely related AAV serotypes. In the present study, we found AAV6 was more efficient in transducing mouse lower airway epithelia in vitro and in vivo than AAV1. To further explore the mechanism of this difference, we found that significantly more AAV1 bound to mouse airway epithelia than AAV6, yet transduction by AAV6 was far superior. Lectin competition assays demonstrated that both AAV1 and AAV6 similarly utilize α-2, 3-, and to a lesser extend α-2, 6- linked sialic acids as the receptors for transduction. Furthermore, the rates of AAV endocytosis could not account for the transduction differences of AAV1 and AAV6. Finally, it was revealed that AAV6 was less susceptible to ubiquitin/proteasome-mediated blocks than AAV1 when transducing mouse airway epithelia. Thus compared with AAV1, AAV6 has a unique ability to escape proteasome-mediated degradation, which is likely responsible for its higher transduction efficiency in mouse airway epithelium.
authors.affiliation: State Key Laboratory for Molecular Virology and Genetic Engineering, Institute of Pathogen Biology at Beijing and The Institute of Blood Transfusion at Chengdu, Chinese Academy of Medical Sciences, 100730 China. lwpzhr@sina.com
authors.forename: Wuping
authors.initials: W
authors.lastname: Li
authors.forename: Liqun
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Wu
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Pickles
authors.forename: R Jude
authors.initials: RJ
authors.lastname: Samulski
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics / Q000502:physiology*; D004705:Endocytosis; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D020545:Respiratory Mucosa / Q000821:virology*; D012794:Sialic Acids / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D011991:Receptors, Virus; D012794:Sialic Acids; D046988:Proteasome Endopeptidase Complex