Canine distemper virus and measles virus fusion glycoprotein trimers: Partial membrane-proximal ectodomain cleavage enhances function

Veronika Von Messling, Dragana Milosevic, Patricia Devaux, Roberto Cattaneo

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The trimeric fusion (F) glycoproteins of morbilliviruses are activated by furin cleavage of the precursor F0 into the F1 and F 2 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.

Original languageEnglish (US)
Pages (from-to)7894-7903
Number of pages10
JournalJournal of virology
Volume78
Issue number15
DOIs
StatePublished - Aug 2004

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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