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Title: Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junin arenavirus envelope glycoprotein

The G2 fusion subunit of the Junin 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.
Authors:
 [1] ;  [2] ;  [3] ;  [4]
  1. Montana Biotechnology Center, University of Montana, Science Complex Room 221, Missoula, MT 59812 (United States). E-mail: joanne.york@umontana.edu
  2. Montana Biotechnology Center, University of Montana, Science Complex Room 221, Missoula, MT 59812 (United States). E-mail: sudhakar.agnihothram@umontana.edu
  3. Instituto de Bioquimica y Biologia Molecular, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata (Argentina) and Departmento de Ciencia y Tecnologia, Universidad Nacional de Quilmes, Bernal (Argentina). E-mail: victor@biol.unlp.edu.ar
  4. Montana Biotechnology Center, University of Montana, Science Complex Room 221, Missoula, MT 59812 (United States). E-mail: jack.nunberg@umontana.edu
Publication Date:
OSTI Identifier:
20779443
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 343; Journal Issue: 2; Other Information: DOI: 10.1016/j.virol.2005.08.030; PII: S0042-6822(05)00520-9; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALANINES; FEVER; GLYCOPROTEINS; MATURATION; MUTAGENESIS; MUTANTS; VIRUSES