Human parainfluenza viruses hPIV1 and hPIV3 bind oligosaccharides with alpha2-3-linked sialic acids that are distinct from those bound by H5 avian influenza virus hemagglutinin

Abstract

We investigated the binding of human parainfluenza virus types 1 and 3 (hPIV1 and hPIV3, respectively) to the glycan array of the Consortium for Functional Glycomics and binding and their release from erythrocytes under conditions where neuraminidase is inactive or active. hPIV1 and hPIV3 bind modifications of Neu5Acalpha2-3Galbeta1-4GlcNAc, including the sialyl-Lewis(x) motif and structures containing 6-sulfogalactose. hPIV1 and hPIV3 thus bind typical N-linked glycans, in contrast to avian influenza virus H5 hemagglutinin (J. Stevens, O. Blixt, T. M. Tumpey, J. K. Taubenberger, J. C. Paulson, and I. A. Wilson, Science 312:404-410, 2006), which binds less-common motifs. While the receptor is not the sole determinant of tropism, hPIV or H5 influenza virus infection of specific cells that express receptors may contribute to their different pathologies.

FIG. 1.

Sodium dodecyl sulfate gel electrophoresis of Alexa-labeled hPIV1 and hPIV3. The fluorescent band (center lane) corresponding to HN is compared to lanes stained with Coomassie blue (left) or Bio-Rad silver reagent (right). Numbers to the left of each panel are molecular masses in kilodaltons.

FIG. 2.

Glycoarray analysis of binding specificities of hPIV1 and hPIV2. Each of the 285 glycans is represented six times on the version 2 printed array. The highest and lowest fluorescence readings were discarded, and the remaining four were averaged. The average binding of virus to each glycan is shown as relative fluorescence units (RFU) ± standard error of the mean.

FIG. 3.

Structures bound by hPIV1 and hPIV3 compared to those bound by H5 HA of A/Vietnam/1203/04. The H5 data and motif were calculated from the work of Stevens et al. (15). (A) Binding calculated as a percentage of total binding; the total includes all glycans that bind >1% of the maximum, excluding glycoproteins. (B) The minimum motifs bound by hPIV1 (top panel), hPIV3 (middle panel), and H5 HA (bottom panel). For hPIV1 and H5 HA the minimal binding units are shaded. For hPIV3 there are three minimal motifs as shown.