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- Title
A Recombinant Sialidase Fusion Protein Effectively Inhibits Human Parainfluenza Viral Infection In Vitro and In Vivo.
- Authors
Moscona, Anne; Porotto, Matteo; Palmer, Samantha; Tai, Caroline; Aschenbrenner, Lori; Triana-Baltzer, Gallen; Qi-Xiang Li; Wurtman, David; Niewiesk, Stefan; Fang Fang
- Abstract
Background. The first step in infection by human parainfluenza viruses (HPIVs) is binding to the surface of respiratory epithelial cells via interaction between viral receptor-binding molecules and sialic acid-containing receptors. DAS181, a recombinant sialidase protein containing the catalytic domain of Actinomyces viscosus sialidase, removes cell surface sialic acid, and we proposed that it would inhibit HPIV infection. Methods. Depletion of sialic acid receptors by DAS181 was evaluated by lectin-binding assays. Anti-HPIV activity in cultured cell lines and in human airway epithelium was assessed by the reduction in viral genomes and/or plaque forming units on treatment. In vivo efficacy of intranasally administered DAS181 was assessed using a cotton rat model. Results. DAS181-mediated desialylation led to anti-HPIV activity in cell lines and human airway epithelium. Intranasal DAS181 in cotton rats, a model for human disease, significantly curtailed infection. Conclusions. Enzymatic removal of the sialic acid moiety of HPIV receptors inhibits infection with all tested HPIV strains, both in vitro and in cotton rats. Enzyme-mediated removal of sialic acid receptors represents a novel antiviral strategy for HPIV. The results of this study raise the possibility of a broad spectrum antiviral agent for influenza virus and HPIVs.
- Subjects
NEURAMINIDASE; PARAINFLUENZA viruses; VIRUS diseases; EPITHELIAL cells; ACTINOMYCES; VIRAL genomes; SIALIC acids; CELL lines; COTTON rats as laboratory animals
- Publication
Journal of Infectious Diseases, 2010, Vol 202, Issue 2, p234
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1086/653621