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Journal of Virology, May 2001, p. 4029-4039, Vol. 75, No. 9
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.9.4029-4039.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Reovirus Binding to Cell Surface Sialic Acid
Potentiates Virus-Induced Apoptosis
Jodi L.
Connolly,1,2
Erik S.
Barton,1,2 and
Terence S.
Dermody1,2,3,*
Departments of Microbiology and
Immunology1 and
Pediatrics3 and Elizabeth B. Lamb Center for Pediatric Research,2 Vanderbilt
University School of Medicine, Nashville, Tennessee 37232
Received 7 November 2000/Accepted 29 January 2001
Reovirus induces apoptosis in cultured cells and in vivo. Genetic
studies indicate that the efficiency with which reovirus strains induce
apoptosis is determined by the viral S1 gene, which encodes attachment
protein
1. However, the biochemical properties of
1 that
influence apoptosis induction are unknown. To determine whether the
capacity of
1 to bind cell surface sialic acid determines the
magnitude of the apoptotic response, we used isogenic reovirus mutants
that differ in the capacity to engage sialic acid. We found that T3SA+,
a virus capable of binding sialic acid, induces high levels of
apoptosis in both HeLa cells and L cells. In contrast, non-sialic-acid-binding strain T3SA
induces little or no apoptosis in
these cell types. Differences in the capacity of T3SA
and T3SA+ to
induce apoptosis are not due to differences in viral protein synthesis
or production of viral progeny. Removal of cell surface sialic acid
with neuraminidase abolishes the capacity of T3SA+ to induce apoptosis.
Similarly, incubation of T3SA+ with sialyllactose, a trisaccharide
comprised of lactose and sialic acid, blocks apoptosis. These findings
demonstrate that reovirus binding to cell surface sialic acid is a
critical requirement for the efficient induction of apoptosis and
suggest that virus receptor utilization plays an important role in
regulating cell death.
*
Corresponding author. Mailing address: Lamb Center for
Pediatric Research, D7235 MCN, Vanderbilt University School of
Medicine, Nashville, TN 37232. Phone: (615) 343-9943. Fax: (615)
343-9723. E-mail:
terry.dermody{at}mcmail.vanderbilt.edu.
Journal of Virology, May 2001, p. 4029-4039, Vol. 75, No. 9
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.9.4029-4039.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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