Lori Aschenbrenner - Academia.edu (original) (raw)
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Università degli Studi di Napoli "Federico II"
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Papers by Lori Aschenbrenner
The Journal of Infectious Diseases, 2010
Background-The first step in infection by human parainfluenza viruses (HPIVs) is binding to the s... more 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 A. 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 (HAE) was assessed by the reduction in viral genomes and/or plaque forming units (PFU) upon 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 HAE. 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.
The Journal of Infectious Diseases, 2010
Background-The first step in infection by human parainfluenza viruses (HPIVs) is binding to the s... more 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 A. 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 (HAE) was assessed by the reduction in viral genomes and/or plaque forming units (PFU) upon 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 HAE. 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.