Signal peptide and helical bundle domains of virulent canine distemper virus fusion protein restrict fusogenicity

Plattet, Philippe; Cherpillod, Pascal; Wiener, Dominique; Zipperle, Ljerka; Vandevelde, Marc; Wittek, Riccardo; Zurbriggen, Andreas (2007). Signal peptide and helical bundle domains of virulent canine distemper virus fusion protein restrict fusogenicity. Journal of virology, 81(20), pp. 11413-25. Baltimore: American Society for Microbiology 10.1128/JVI.01287-07

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Persistence in canine distemper virus (CDV) infection is correlated with very limited cell-cell fusion and lack of cytolysis induced by the neurovirulent A75/17-CDV compared to that of the cytolytic Onderstepoort vaccine strain. We have previously shown that this difference was at least in part due to the amino acid sequence of the fusion (F) protein (P. Plattet, J. P. Rivals, B. Zuber, J. M. Brunner, A. Zurbriggen, and R. Wittek, Virology 337:312-326, 2005). Here, we investigated the molecular mechanisms of the neurovirulent CDV F protein underlying limited membrane fusion activity. By exchanging the signal peptide between both F CDV strains or replacing it with an exogenous signal peptide, we demonstrated that this domain controlled intracellular and consequently cell surface protein expression, thus indirectly modulating fusogenicity. In addition, by serially passaging a poorly fusogenic virus and selecting a syncytium-forming variant, we identified the mutation L372W as being responsible for this change of phenotype. Intriguingly, residue L372 potentially is located in the helical bundle domain of the F(1) subunit. We showed that this mutation drastically increased fusion activity of F proteins of both CDV strains in a signal peptide-independent manner. Due to its unique structure even among morbilliviruses, our findings with respect to the signal peptide are likely to be specifically relevant to CDV, whereas the results related to the helical bundle add new insights to our growing understanding of this class of F proteins. We conclude that different mechanisms involving multiple domains of the neurovirulent A75/17-CDV F protein act in concert to limit fusion activity, preventing lysis of infected cells, which ultimately may favor viral persistence.

Item Type:	Journal Article (Original Article)
Division/Institute:	05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research 05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DVK - Clinical Research [discontinued] 05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Clinical Neurology
UniBE Contributor:	Plattet, Philippe, Wiener, Dominique Judith, Zipperle, Ljerka, Vandevelde, Marc, Zurbriggen, Andreas (A)
ISSN:	0022-538X
Publisher:	American Society for Microbiology
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:52
Last Modified:	29 Mar 2023 23:32
Publisher DOI:	10.1128/JVI.01287-07
PubMed ID:	17686846
Web of Science ID:	000250019400055
URI:	https://boris.unibe.ch/id/eprint/22258 (FactScience: 33624)