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Virology. 2005 Dec 20;343(2):267-74. Epub 2005 Sep 16.

Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junín arenavirus envelope glycoprotein.

Author information

1
Montana Biotechnology Center, The University of Montana, Science Complex Room 221, Missoula, MT 59812, USA. joanne.york@umontana.edu

Abstract

The G2 fusion subunit of the Junín virus envelope glycoprotein GP-C contains two hydrophobic heptad-repeat regions that are postulated to form a six-helix bundle structure required for the membrane fusion activity of Class I viral fusion proteins. We have investigated the role of these heptad-repeat regions and, specifically, the importance of the putative interhelical a and d position sidechains by using alanine-scanning mutagenesis. All the mutant glycoproteins were expressed and transported to the cell surface. Proteolytic maturation at the subtilisin kexin isozyme-1/site-1-protease (SKI-1/S1P) cleavage site was observed in all but two of the mutants. Among the adequately cleaved mutant glycoproteins, four positions in the N-terminal region (I333, L336, L347 and L350) and two positions in the C-terminal region (R392 and W395) were shown to be important determinants of cell-cell fusion. Taken together, our results indicate that alpha-helical coiled-coil structures are likely critical in promoting arenavirus membrane fusion. These findings support the inclusion of the arenavirus GP-C among the Class I viral fusion proteins and suggest pharmacologic and immunologic strategies for targeting arenavirus infection and hemorrhagic fever.

PMID:
16169032
DOI:
10.1016/j.virol.2005.08.030
[Indexed for MEDLINE]
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