Functional interactions between the fusion protein and hemagglutinin-neuraminidase of human parainfluenza viruses

Abstract

The fusion glycoprotein (F) and hemagglutinin-neuraminidase (HN) genes of human parainfluenza virus type 2 (P12) were molecularly cloned and expressed in HeLa-T4 cells by using the vaccinia virus-T7 transient expression system. Expression of the F and HN proteins was detected by using immunoprecipitation and surface inmunofluorescence staining. Although the F protein was found to be cleaved into F1 and F2 and expressed on cell surfaces, no cell fusion was observed. However, cotransfection of the F-protein gene together with the P12 HN gene resulted in significant levels of cell fusion. Cell fusion was also observed when separate cell cultures were transfected with the HN and F genes and the F-expressing ceLls were mixed with the HN-expressing cells. Surprisingly, when the PI2 F protein was expressed together with the parainfluenza virus type 3 (P13) HN protein, no fusion was detectable in the transfected cells. Similarly, no fusion was found upon coexpression of the P12 HN and P13 F proteins. However, coexpression of the PI3 F and HN proteins resulted in extensive cell fusion, which resembled the P12 coexpression result. These results indicate that under the conditions used, the F protein is unable to cause fusion by itself and the HN protein provides a specific function in cell fusion which cannot be provided by another paramyxovirus attachment protein. Further, the results suggest that a type-specific functional interaction between the F and HN proteins is involved in mediating cell fusion.

Roles of the Fusion and Hemagglutinin-Neuraminidase Proteins in Replication, Tropism, and Pathogenicity of Avian Paramyxoviruses

“…In most paramyxoviruses, the homotypic F and HN glycoproteins have been known to be physically associated with each other on the cell surface, indicating the attachment proteindependent mode of fusion (13,57). We found that the substitution of NDV F protein alone into rAPMV-2 conferred the ability to replicate in the brains of 1-day-old chicks when infected via the intracerebral route, indicative of neurotropism, or via the intranasal route, indicative of neuroinvasiveness.…”

Truncation of the COOH-terminal region of the paramyxovirus SV5 fusion protein leads to hemifusion but not complete fusion.

“…It has become increasingly clear that there is a difference in the requirements for fusion among different paramyxoviruses (Bagai and Lamb, 1995b;. Whereas most of the paramyxoviruses require the coexpression of homotypic F and HN proteins in order to induce cell-cell fusion (Ebata et al, 1991;Hu et al, 1992;Morrison et al, 1991;Sergel et al, 1993;Tanabayashi et al, 1992;Wild et al, 1991), a homotypic HN protein is not essential for SV5 F protein-mediated cell fusion (Bagai and Lamb, 1995b). Further evidence for the sufficiency of SV5 F protein in cell fusion comes from the finding that F mutants containing single Gly to Ala changes in the fusion peptide cause a remarkable increase in the syncytia formation compared to the wild-type (wt) F protein Ward et al, 1995).…”

Neurokinin-1 enables measles virus trans-synaptic spread in neurons

“…Based on this observation, we next wanted to establish what role, if any, the viral fusion protein played in trans-synaptic transport. While it is generally believed that H and F have interaction domains that coordinate receptor binding and fusion (Hu, Ray, and Compans, 1992), work by other laboratories has suggested that F may act independently of H, and may even govern target cell specificity. For example, in simian virus 5 (SV5), F promotes fusion in the absence of the hemagglutinin-neuraminidase (HN) protein, albeit less efficiently than when HN is present (Horvath et al, 1992;Ito et al, 1997).…”