The Interferon-Inducible Proteoglycan Testican-2/SPOCK2 Functions as a Protective Barrier against Virus Infection of Lung Epithelial Cells

Abstract

Here we report a novel proteoglycan protein, testican-2/SPOCK2, that prevents influenza virus infection. Testican-2/SPOCK2 is a complex type of secreted proteoglycan with heparan sulfate GAG chains attached to the core protein. SPOCK2 expression is induced upon virus infection or by interferons, and the protein is secreted to an extracellular compartment, where it acts directly to block virus-cell attachment and entry. Treatment with purified testican-2/SPOCK2 protein can efficiently block influenza virus infection in vitro and in vivo . We also identified the heparan sulfate moiety as a key regulatory module for this inhibitory effect. Based on its mode of action (cell attachment/entry blocker) and site of action (extracellular compartment), we propose testican-2/SPOCK2 as a potential antiviral agent that can efficiently control influenza virus infection.