The hemagglutinin-neuraminidase glycoproteins of human parainfluenza virus type 1 and Sendai virus have high structure-function similarity with limited antigenic cross-reactivity.

Human parainfluenza virus type 1 (hPIV-1) is closely related to Sendai virus on the basis of cross-reactivity of antisera. We examined this association further by using monoclonal antibodies to the Sendai virus hemagglutinin-neuraminidase (HN) glycoprotein to determine the relationship between overall protein structure and the hemagglutination and neuraminidase functions. Of 10 monoclonal antibodies representing four nonoverlapping antigenic sites on the HN of Sendai virus, only 4 from two sites cross-reacted with hPIV-1, indicating a limited conservation of epitopes. One of these four inhibited the hemagglutinating activity of hPIV-1 comparably to Sendai virus, but none appreciably inhibited the neuraminidase activity of hPIV-1. The ability of some of these monoclonal antibodies to inhibit only hemagglutinating or neuraminidase activity of either virus provided evidence for two separate active sites on the HN molecule. To determine the overall structural relationship of the HNs of hPIV-1 and Sendai virus, we cloned and sequenced the HN gene of hPIV-1. The HN clone was made from genomic RNA and was identified by hybrid-arrested in vitro translation of mRNA. The predicted HN protein sequence of hPIV-1 was identical in length to that of Sendai virus and had a shared identity of 72%. There was a marked conservation of structural elements (cysteines, prolines, and glycines), which would predict a similar molecular conformation. However, there were 10 potential glycosylation sites on the HN of hPIV-1, compared with 5 on Sendai virus. Some of these sites may be responsible for the inability of the Sendai virus monoclonal antibodies to cross-react. The results of our study support a close structure-function relationship between hPIV-1 and Sendai virus but suggest limited antigenic cross-reactivity.