A recombinant sialidase fusion protein effectively inhibits human parainfluenza viral infection in vitro and in vivo.

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.

• Authors: Anne Moscona, Matteo Porotto, Samantha Palmer, Caroline Tai, Lori Aschenbrenner, Gallen Triana-Baltzer, Qi-Xiang Li, David Wurtman, Stefan Niewiesk, Fang Fang
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 202 Issue 2 Pg. 234-41 (Jul 15 2010) ISSN: 1537-6613 [Electronic] United States
• PMID: 20533871 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• AREG protein, human
• Amphiregulin
• Areg protein, rat
• EGF Family of Proteins
• Glycoproteins
• Intercellular Signaling Peptides and Proteins
• P protein, Human parainfluenza virus 2
• Phosphoproteins
• Receptors, Cell Surface
• Recombinant Fusion Proteins
• Viral Proteins
• sialic acid receptor
• oplunofusp
• Neuraminidase

Topics

• Amphiregulin
• Animals
• Cell Line
• Disease Models, Animal
• EGF Family of Proteins
• Enzyme-Linked Immunosorbent Assay
• Glycoproteins (genetics)
• Humans
• Intercellular Signaling Peptides and Proteins (genetics)
• Lymphocyte Depletion
• Neuraminidase (genetics)
• Paramyxoviridae Infections (enzymology, immunology)
• Phosphoproteins (immunology)
• Rats
• Receptors, Cell Surface (genetics)
• Recombinant Fusion Proteins (pharmacology)
• Sigmodontinae
• Trachea (immunology, virology)
• Viral Plaque Assay
• Viral Proteins (immunology)