Journal of General Virology, Vol 80, 107-115, Copyright © 1999 by Society for General Microbiology

ARTICLES

Alternative mechanisms of interaction between homotypic and heterotypic parainfluenza virus HN and F proteins

S Tong and RW Compans
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.

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.

This article has been cited by other articles:

				L. W. McGinnes and T. G. Morrison Inhibition of Receptor Binding Stabilizes Newcastle Disease Virus HN and F Protein-Containing Complexes J. Virol., March 15, 2006; 80(6): 2894 - 2903. [Abstract] [Full Text] [PDF]

				K. A. Gravel and T. G. Morrison Interacting Domains of the HN and F Proteins of Newcastle Disease Virus J. Virol., October 15, 2003; 77(20): 11040 - 11049. [Abstract] [Full Text] [PDF]

				L. W. McGinnes, K. Gravel, and T. G. Morrison Newcastle Disease Virus HN Protein Alters the Conformation of the F Protein at Cell Surfaces J. Virol., November 13, 2002; 76(24): 12622 - 12633. [Abstract] [Full Text] [PDF]

				K. N. Bossart, L.-F. Wang, M. N. Flora, K. B. Chua, S. K. Lam, B. T. Eaton, and C. C. Broder Membrane Fusion Tropism and Heterotypic Functional Activities of the Nipah Virus and Hendra Virus Envelope Glycoproteins J. Virol., October 11, 2002; 76(22): 11186 - 11198. [Abstract] [Full Text] [PDF]

				R. K. Plemper, A. L. Hammond, and R. Cattaneo Measles Virus Envelope Glycoproteins Hetero-oligomerize in the Endoplasmic Reticulum J. Biol. Chem., November 16, 2001; 276(47): 44239 - 44246. [Abstract] [Full Text] [PDF]

				M. B. Stope, A. Karger, U. Schmidt, and U. J. Buchholz Chimeric Bovine Respiratory Syncytial Virus with Attachment and Fusion Glycoproteins Replaced by Bovine Parainfluenza Virus Type 3 Hemagglutinin-Neuraminidase and Fusion Proteins J. Virol., October 1, 2001; 75(19): 9367 - 9377. [Abstract] [Full Text] [PDF]

				U. J. Buchholz, H. Granzow, K. Schuldt, S. S. Whitehead, B. R. Murphy, and P. L. Collins Chimeric Bovine Respiratory Syncytial Virus with Glycoprotein Gene Substitutions from Human Respiratory Syncytial Virus (HRSV): Effects on Host Range and Evaluation as a Live-Attenuated HRSV Vaccine J. Virol., February 1, 2000; 74(3): 1187 - 1199. [Abstract] [Full Text]