1887

Abstract

Cell fusion by human parainfluenza virus (HPIV) type 2 or type 3 requires the coexpression of both the fusion (F) and haemagglutinin-neuraminidase (HN) glycoproteins from the same virus type, indicating that promotion of fusion requires a type-specific interaction between F and HN. In this report we have further investigated the interaction of the ectodomains of the F and HN glycoproteins from HPIV2 and HPIV3. We constructed mutants of the HPIV2 F and HPIV3 F proteins (F′-KDEL) lacking a transmembrane anchor and a cytoplasmic tail, and containing a C-terminal signal for retention in the endoplasmic reticulum (ER). The P12 and P13 F′-KDEL proteins were both found to be retained intracellularly, and neither could induce cell fusion when co-expressed with homotypic HN proteins. Qualitative and quantitative cell-fusion assays also showed that both the P12 F′-KDEL and P13 F′-KDEL proteins have inhibitory effects on P12 F- and HN-induced cell fusion. However, the F-KDEL mutants were found to inhibit cell fusion by two distinct mechanisms. An interaction between P12 F′-KDEL and P12 HN results in intracellular retention of HN, and a block in its transport to the cell surface. In contrast, P13 F′-KDEL was found to suppress the steady-state intracellular expression levels of HPIV2 HN. These results support the conclusion that fusion involves an interaction between the HN and F proteins, and suggest that an association between F and HN may occur in the ER.

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1999-01-01
2022-05-28
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