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 inhaled pathogens with the lectin domains of SP-D. Respiratory syncytial virus (RSV), the most important viral pathogen of neonates and infants, encodes a highly glycosylated attachment protein, G. Binding studies were performed with G protein from RSV (human, A2 strain) and both native and recombinant human 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 bind to RSV G protein in a concentration-dependent manner. Both EDTA and mannan inhibited binding of full-length SP-D. These results indicate that binding occurs via the carbohydrate recognition domain of the SP-D. The recombinant SP-D inhibited RSV infectivity in cell culture in a dose-dependent manner, giving 100% inhibition of replication. Intranasal administration of recombinant SP-D to RSV-infected mice inhibited replication of the virus in the lungs, reducing levels of lung virus by 80%. These results suggest that SP-D plays a major role in clearing RSV from the lungs.
Hickling
T P
TP
GlaxoWellcome Medicines Research Centre, Stevenage, GB. tph94318@glaxowellcome.co.uk
Bright
H
H
Wing
K
K
Gower
D
D
Martin
S L
SL
Sim
R B
RB
Malhotra
R
R
D000818:Animals; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D006023:Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D015707:HN Protein; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000378:metabolism* / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D018113:Respiratory Syncytial Virus, Human / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
D006023:Glycoproteins; D015707:HN Protein; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G