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Journal of Virology, October 1999, p. 8907-8912, Vol. 73, No. 10
Department of Pathobiological Sciences,
School of Veterinary Medicine, University of Wisconsin
Received 16 February 1999/Accepted 14 July 1999
Ebola viruses contain a single glycoprotein (GP) spike, which
functions as a receptor binding and membrane fusion protein. It
contains a highly conserved hydrophobic region (amino acids 524 to 539)
located 24 amino acids downstream of the N terminus of the Ebola virus
GP2 subunit. Comparison of this region with the structural features of
the transmembrane subunit of avian retroviral GPs suggests that the
conserved Ebola virus hydrophobic region may, in fact, serve as the
fusion peptide. To test this hypothesis directly, we introduced
conservative (alanine) and nonconservative (arginine) amino acid
substitutions at eight positions in this region of the GP2 molecule.
The effects of these mutations were deduced from the ability of the
Ebola virus GP to complement the infectivity of a vesicular stomatitis
virus (VSV) lacking the receptor-binding G protein. Some mutations,
such as Ile-to-Arg substitutions at positions 532 (I532R), F535R,
G536A, and P537R, almost completely abolished the ability of the GP to
support VSV infectivity without affecting the transport of GP to the
cell surface and its incorporation into virions or the production of virus particles. Other mutations, such as G528R, L529A, L529R, I532A,
and F535A, reduced the infectivity of the VSV-Ebola virus pseudotypes
by at least one-half. These findings, together with previous reports of
liposome association with a peptide corresponding to positions 524 to
539 in the GP molecule, offer compelling support for a fusion peptide
role for the conserved hydrophobic region in the Ebola virus GP.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Mutational Analysis of the Putative Fusion Domain
of Ebola Virus Glycoprotein
Madison,
Madison, Wisconsin 537061; Special
Pathogens Branch, Division of Viral and Rickettsial Diseases, National
Center for Infectious Disease, Centers for Disease Control and
Prevention, Atlanta, Georgia 303332; and
Department of Microbiology and Immunology, University of
Tennessee, Memphis, Tennessee 381633
*
Corresponding author. Mailing address: Department of
Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin
Madison, 2015 Linden Dr. West, Madison, WI 53706. Phone: (608) 265-4925. Fax: (608) 265-5622. E-mail:
kawaokay{at}svm.vetmed.wisc.edu.
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