title: Expression of an engineered soluble coxsackievirus and adenovirus receptor by a dimeric AAV9 vector inhibits adenovirus infection in mice.
abstract: Immunosuppressed (IS) patients, such as recipients of hematopoietic stem cell transplantation, occasionally develop severe and fatal adenovirus (Ad) infections. Here, we analyzed the potential of a virus receptor trap based on a soluble coxsackievirus and Ad receptor (sCAR) for inhibition of Ad infection. In vitro, a dimeric fusion protein, sCAR-Fc, consisting of the extracellular domain of CAR and the Fc portion of human IgG1 and a monomeric sCAR lacking the Fc domain, were expressed in cell culture. More sCAR was secreted into the cell culture supernatant than sCAR-Fc, but it had lower Ad neutralization activity than sCAR-Fc. Further investigations showed that sCAR-Fc reduced the Ad infection by a 100-fold and Ad-induced cytotoxicity by ~20-fold. Not only was Ad infection inhibited by sCAR-Fc applied prior to infection, it also inhibited infection when used to treat ongoing Ad infection. In vivo, sCAR-Fc was delivered to IS mice by an AAV9 vector, resulting in persistent and high (>40 μg ml(-1)) sCAR-Fc serum levels. The sCAR-Fc serum concentration was sufficient to significantly inhibit hepatic and cardiac wild-type Ad5 infection. Treatment with sCAR-Fc did not induce side effects. Thus, sCAR-Fc virus receptor trap may be a promising novel therapeutic for treatment of Ad infections.
authors: Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Gustav-Meyer-Allee 25, Berlin, Germany.
authors: C
authors: C
authors: Röger
authors: Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Gustav-Meyer-Allee 25, Berlin, Germany.
authors: T
authors: T
authors: Pozzuto
authors: Department of Vetrinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Strasse 15, Berlin, Germany.
authors: R
authors: R
authors: Klopfleisch
authors: Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Gustav-Meyer-Allee 25, Berlin, Germany.
authors: J
authors: J
authors: Kurreck
authors: Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Gustav-Meyer-Allee 25, Berlin, Germany.
authors: S
authors: S
authors: Pinkert
authors: Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Gustav-Meyer-Allee 25, Berlin, Germany.
authors: H
authors: H
authors: Fechner
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000257:Adenoviridae Infections / Q000628:therapy*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D000229:Dependovirus / Q000378:metabolism; D004770:Enterovirus / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use
chemical_list: D002352:Carrier Proteins; D011991:Receptors, Virus; D011994:Recombinant Proteins; C085301:adenovirus receptor; C029702:prolactin-binding protein