A recombinant trimeric surfactant protein D carbohydrate recognition domain inhibits respiratory syncytial virus infection in vitro and in vivo

The pulmonary collectin, lung surfactant protein D (SP-D), plays a role in host defense mediated by the interaction of surface carbohydrates of inhale d pathogens with the lectin domains of SP-D. Respiratory syncytial virus (R SV), the most important viral pathogen of neonates and infants, encodes a h ighly glycosylated attachment protein, G. Binding studies were performed wi th G protein from RSV (human, A2 strain) and both native and recombinant hu man SP-D. The effect of recombinant trimeric SP-D lectin domains (rSP-D) on the interaction between RSV and host cells was determined by two methods: an infectivity study with monolayers of Hep-2C cells and in vivo infections in BALB/c mice. These studies show that full-length and recombinant SP-D b ind to RSV G protein in a concentration-dependent manner. Both EDTA and man nan inhibited binding of full-length SP-D. These results indicate that bind ing occurs via the carbohydrate recognition domain of the SP-D. The recombi nant SP-D inhibited RSV infectivity in cell culture in a dose-dependent man ner, giving 100% inhibition of replication. Intranasal administration of re combinant SP-D to RSV-infected mice inhibited replication of the virus in t he lungs, reducing levels of lung virus by 80%. These results suggest that SP-D plays a major role in clearing RSV from the lungs.