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Journal of Virology, November 2001, p. 11196-11204, Vol. 75, No. 22
Molecular Virology Section, Department of
Medical Microbiology, University of Groningen, 9713 AV Groningen,
The Netherlands1; Department of
Microbiology and Immunology, School of Medicine, University of
North Carolina at Chapel Hill, Chapel Hill, North Carolina
27599-72902; and Department of
Chemistry and Biochemistry, Queens College of the City University
of New York, Flushing, New York 113673
Received 25 June 2001/Accepted 16 August 2001
The spike glycoprotein E2 of Sindbis virus (SIN) is synthesized in
the infected cell as a PE2 precursor protein, which matures through cleavage by a cellular furin-like protease. Previous work has
shown that SIN mutants impaired in PE2 cleavage are noninfectious on BHK-21 cells, the block in infection being localized at a step after
virus-receptor interaction but prior to RNA replication. Here, we
studied the membrane fusion properties of SIN PE2 cleavage mutants
and observed that these viruses are impaired in their ability to form
an E1 homotrimer and to fuse with liposomes at a mildly acidic pH. The
block in spike rearrangement and fusion could be overridden by
exposure of the mutant viruses to very low pH (<4.5). Cleavage mutants
with second-site resuscitating mutations in PE2 were highly
infectious for BHK-21 cells. The ability of these viruses to form E1
homotrimers and to fuse at a mildly acidic pH was completely
restored despite a sustained lack of PE2 cleavage.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.22.11196-11204.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
PE2 Cleavage Mutants of Sindbis Virus: Correlation between Viral
Infectivity and pH-Dependent Membrane Fusion Activation of the
Spike Heterodimer
*
Corresponding author. Mailing address: Department of
Medical Microbiology, Molecular Virology Section, University of
Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Phone: 31 50 3632733. Fax: 31 50 3638171. E-mail:
J.C.Wilschut{at}med.rug.nl.
Journal of Virology, November 2001, p. 11196-11204, Vol. 75, No. 22
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.22.11196-11204.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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