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.