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Title: Effect of specific amino acid substitutions in the putative fusion peptide of structural glycoprotein E2 on Classical Swine Fever Virus replication

E2, along with E{sup rns} and E1, is an envelope glycoprotein of Classical Swine Fever Virus (CSFV). E2 is involved in several virus functions: cell attachment, host range susceptibility and virulence in natural hosts. Here we evaluate the role of a specific E2 region, {sup 818}CPIGWTGVIEC{sup 828}, containing a putative fusion peptide (FP) sequence. Reverse genetics utilizing a full-length infectious clone of the highly virulent CSFV strain Brescia (BICv) was used to evaluate how individual amino acid substitutions within this region of E2 may affect replication of BICv. A synthetic peptide representing the complete E2 FP amino acid sequence adopted a β-type extended conformation in membrane mimetics, penetrated into model membranes, and perturbed lipid bilayer integrity in vitro. Similar peptides harboring amino acid substitutions adopted comparable conformations but exhibited different membrane activities. Therefore, a preliminary characterization of the putative FP {sup 818}CPIGWTGVIEC{sup 828} indicates a membrane fusion activity and a critical role in virus replication. - Highlights: • A putative fusion peptide (FP) region in CSFV E2 protein was shown to be critical for virus growth. • Synthetic FPs were shown to efficiently penetrate into lipid membranes using an in vitro model. • Individual residues in the FP affecting virusmore » replication were identified by reverse genetics. • The same FP residues are also responsible for mediating membrane fusion.« less
Authors:
 [1] ;  [2] ; ;  [1] ;  [1] ;  [3] ;  [1] ;  [4] ;  [5] ;  [2] ;  [1]
  1. Plum Island Animal Disease Center, ARS, USDA (United States)
  2. Biophysics Unit (CSIC-UPV/EHU), Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao (Spain)
  3. (United States)
  4. Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), E-08003 Barcelona (Spain)
  5. Plum Island Animal Disease Center, DHS, Greenport, NY 11944 (United States)
Publication Date:
OSTI Identifier:
22435035
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 456-457; Other Information: Copyright (c) 2014 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; AMINO ACID SEQUENCE; AMINO ACIDS; COMPARATIVE EVALUATIONS; FEVER; GENETICS; GLYCOPROTEINS; HARBORS; HOST; IN VITRO; LIPIDS; MEMBRANES; PEPTIDES; PLANT GROWTH; RESIDUES; SWINE; VIRULENCE; VIRUSES