Canine Distemper Virus and Measles Virus Fusion Glycoprotein Trimers: Partial Membrane-Proximal Ectodomain Cleavage Enhances Function
Year: 2004
Type: article
Abstract: The trimeric fusion (F) glycoproteins of morbilliviruses are activated by furin cleavage of the precursor F(0) into the F(1) 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 F(0) into the F(1) and F(2) subunits, producing F(1a) and F(1b) fragments that are incorporated in viral particles. We also detected the F(1b) 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 F(1a/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.
Source: Journal of Virology
Authors: Veronika von Messling, Dragana Milosevic, Patricia Devaux, Roberto Cattaneo
Institution: Mayo Clinic
Language: English
Topic: Virology and Viral Diseases
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2141627198