title: Native and engineered tropism of vectors derived from a rare species D adenovirus serotype 43.
abstract: Unique molecular properties of species D adenoviruses (Ads)-the most diverse yet underexplored group of Ads-have been used to develop improved gene vectors. The low seroprevalence in humans of adenovirus serotype 43 (Ad43), an otherwise unstudied species D Ad, identified this rare serotype as an attractive new human gene therapy vector platform. Thus, in this study we wished to assess biological properties of Ad43 essential to its vectorization. We found that (1) Ad43 virions do not bind blood coagulation factor X and cause low random transduction upon vascular delivery; (2) they clear host tissues more quickly than do traditionally used Ad5 vectors; (3) Ad43 uses CD46 as primary receptor; (4) Ad43 can use integrins as alternative primary receptors. As the first step toward vectorization of Ad43, we demonstrated that the primary receptor specificity of the Ad43 fiber can be altered to achieve infection via Her2, an established oncotarget. Whereas this modification required use of the Ad5 fiber shaft, the presence of this domain in chimeric virions did not make them susceptible for neutralization by anti-Ad5 antibodies.
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Natalya
authors.initials: N
authors.lastname: Belousova
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Galina
authors.initials: G
authors.lastname: Mikheeva
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Chiyi
authors.initials: C
authors.lastname: Xiong
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Center for Biomolecular Structure and Function, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Loren J
authors.initials: LJ
authors.lastname: Stagg
authors.affiliation: Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gagea
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Fox
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Roland L
authors.initials: RL
authors.lastname: Bassett
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Center for Biomolecular Structure and Function, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.|Current address: University of Leeds, Leeds, United Kingdom.
authors.forename: John E
authors.initials: JE
authors.lastname: Ladbury
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tuebingen, Tuebingen, Germany.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Braun
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tuebingen, Tuebingen, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Stehle
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Krasnykh
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice
keywords: CD46; adenovirus; serotype; targeting; tropism