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Journal of Virology, October 2000, p. 9738-9741, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Critical Role for the Cysteines Flanking the Internal Fusion
Peptide of Avian Sarcoma/Leukosis Virus Envelope
Glycoprotein
S. E.
Delos* and
J. M.
White
Department of Cell Biology, School of
Medicine, University of Virginia Health System, Charlottesville,
Virginia 22908
Received 11 April 2000/Accepted 28 July 2000
The transmembrane subunit (TM) of the envelope glycoprotein (Env)
of the oncovirus avian sarcoma/leukosis virus (ASLV) contains an
internal fusion peptide flanked by two cysteines (C9 and C45). These
cysteines, as well as an analogous pair in the Ebola virus GP
glycoprotein, are predicted to be joined by a disulfide bond. To
examine the importance of these cysteines, we mutated C9 and C45 in the
ASLV subtype A Env (EnvA), individually and together, to serine. All of
the mutant EnvAs formed trimers that were composed of the
proteolytically processed surface (SU) and TM subunits. All mutant
EnvAs were incorporated into murine leukemia virus pseudotyped virions
and bound receptor with wild-type affinity. Nonetheless, all mutant
EnvAs were significantly impaired (~1,000-fold) in their ability to
support infectivity. They were also significantly impaired in their
ability to mediate cell-cell fusion. Our data are consistent with a
model in which the internal fusion peptide of ASLV-A EnvA exists as a
loop that is stabilized by a disulfide bond at its base and in which
this stabilized loop serves an important function during virus-cell
fusion. The fusion peptide of the Ebola virus GP glycoprotein may
conform to a similar structure.
*
Corresponding author. Mailing address: Department of
Cell Biology, University of Virginia Health System, School of Medicine, P.O. Box 800732, Charlottesville, VA 22908-0732. Phone: (804) 924-2009. Fax: (804) 982-3912. E-mail:
sed7a{at}unix.mail.virginia.edu.
Journal of Virology, October 2000, p. 9738-9741, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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