title: A new human DSG2-transgenic mouse model for studying the tropism and pathology of human adenoviruses.
abstract: We have recently reported that a group of human adenoviruses (HAdVs) uses desmoglein 2 (DSG2) as a receptor for infection. Among these are the widely distributed serotypes HAdV-B3 and HAdV-B7, as well as a newly emerged strain derived from HAdV-B14. These serotypes do not infect rodent cells and could not up until now be studied in small-animal models. We therefore generated transgenic mice containing the human DSG2 locus. These mice expressed human DSG2 (hDSG2) at a level and in a pattern similar to those found for humans and nonhuman primates. As an initial application of hDSG2-transgenic mice, we used a green fluorescent protein (GFP)-expressing HAdV-B3 vector (Ad3-GFP) and studied GFP transgene expression by quantitative reverse transcription-PCR (qRT-PCR) and immunohistochemistry subsequent to intranasal and intravenous virus application. After intranasal application, we found efficient transduction of bronchial and alveolar epithelial cells in hDSG2-transgenic mice. Intravenous Ad3-GFP injection into hDSG2-transgenic mice resulted in hDSG2-dependent transduction of epithelial cells in the intestinal and colon mucosa. Our findings give an explanation for clinical symptoms associated with infection by DSG2-interacting HAdVs and provide a rationale for using Ad3-derived vectors in gene therapy.
authors.affiliation: Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Wang
authors.forename: Ines
authors.initials: I
authors.lastname: Beyer
authors.forename: Jonas
authors.initials: J
authors.lastname: Persson
authors.forename: Hui
authors.initials: H
authors.lastname: Song
authors.forename: ZongYi
authors.initials: Z
authors.lastname: Li
authors.forename: Maximilian
authors.initials: M
authors.lastname: Richter
authors.forename: Hua
authors.initials: H
authors.lastname: Cao
authors.forename: Ruan
authors.initials: R
authors.lastname: van Rensburg
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Yao
authors.forename: Kelly
authors.initials: K
authors.lastname: Hudkins
authors.forename: Roma
authors.initials: R
authors.lastname: Yumul
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Zhang
authors.forename: Mujun
authors.initials: M
authors.lastname: Yu
authors.forename: Pascal
authors.initials: P
authors.lastname: Fender
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
authors.forename: André
authors.initials: A
authors.lastname: Lieber
mesh_terms: D000258:Adenovirus Infections, Human / Q000473:pathology* / Q000821:virology; D000260:Adenoviruses, Human / Q000472:pathogenicity*; D000818:Animals; D051301:Desmoglein 2 / Q000235:genetics*; D004195:Disease Models, Animal; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D011991:Receptors, Virus / Q000235:genetics*; D013194:Staining and Labeling / Q000379:methods; D014161:Transduction, Genetic; D056189:Viral Tropism
chemical_list: C495314:DSG2 protein, human; D051301:Desmoglein 2; D011991:Receptors, Virus; D049452:Green Fluorescent Proteins