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Journal of Virology, August 2004, p. 7894-7903, Vol. 78, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.15.7894-7903.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Canine Distemper Virus and Measles Virus Fusion Glycoprotein Trimers: Partial Membrane-Proximal Ectodomain Cleavage Enhances Function

Veronika von Messling,1,{dagger} Dragana Milosevic,1 Patricia Devaux,1 and Roberto Cattaneo1,2*

Molecular Medicine Program,1 Virology and Gene Therapy Graduate Track, Mayo Clinic College of Medicine, Rochester, Minnesota2

Received 9 February 2004/ Accepted 31 March 2004

The trimeric fusion (F) glycoproteins of morbilliviruses are activated by furin cleavage of the precursor F0 into the F1 and F2 subunits. Here we show that an additional membrane-proximal cleavage occurs and modulates F protein function. We initially observed that the ectodomain of approximately one in three measles virus (MV) F proteins is cleaved proximal to the membrane. Processing occurs after cleavage activation of the precursor F0 into the F1 and F2 subunits, producing F1a and F1b fragments that are incorporated in viral particles. We also detected the F1b fragment, including the transmembrane domain and cytoplasmic tail, in cells expressing the canine distemper virus (CDV) or mumps virus F protein. Six membrane-proximal amino acids are necessary for efficient CDV F1a/b cleavage. These six amino acids can be exchanged with the corresponding MV F protein residues of different sequence without compromising function. Thus, structural elements of different sequence are functionally exchangeable. Finally, we showed that the alteration of a block of membrane-proximal amino acids results in diminished fusion activity in the context of a recombinant CDV. We envisage that selective loss of the membrane anchor in the external subunits of circularly arranged F protein trimers may disengage them from pulling the membrane centrifugally, thereby facilitating fusion pore formation.

* Corresponding author. Mailing address: Molecular Medicine Program, Mayo Clinic, Guggenheim 1838, 200 1st St. SW, Rochester, MN 55905. Phone: (507) 284-0171. Fax: (507) 266-2122. E-mail: cattaneo.roberto{at}mayo.edu.

{dagger} Present address: INRS-Institut Armand-Frappier, Universite du Quebec, Quebec, Laval H7V 1B7, Canada.

Journal of Virology, August 2004, p. 7894-7903, Vol. 78, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.15.7894-7903.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Malik, T., Wolbert, C., Mauldin, J., Sauder, C., Carbone, K. M., Rubin, S. A. (2007). Functional consequences of attenuating mutations in the haemagglutinin neuraminidase, fusion and polymerase proteins of a wild-type mumps virus strain. J. Gen. Virol. 88: 2533-2541 [Abstract] [Full Text]  
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  • Springfeld, C., von Messling, V., Tidona, C. A., Darai, G., Cattaneo, R. (2005). Envelope Targeting: Hemagglutinin Attachment Specificity Rather than Fusion Protein Cleavage-Activation Restricts Tupaia Paramyxovirus Tropism. J. Virol. 79: 10155-10163 [Abstract] [Full Text]  


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