Journal of Virology, May 2001, p. 4604-4613, Vol. 75, No. 10
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.10.4604-4613.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 381051; Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526,2 and Central Blood Center, Japanese Red Cross, 4-1-31 Hiroo, Shibuya-ku, Tokyo 150-0012,4 Japan; and Department of Pathology, The Health Science Center, University of Tennessee, Memphis, Tennessee 381633
Received 6 November 2000/Accepted 13 February 2001
Through their hemagglutinin-neuraminidase glycoprotein,
parainfluenza viruses bind to sialic acid-containing glycoconjugates to
initiate infection. Although the virus-receptor interaction is a key
factor of infection, the exact nature of the receptors that human
parainfluenza viruses recognize has not been determined. We evaluated
the abilities of human parainfluenza virus types 1 (hPIV-1) and 3 (hPIV-3) to bind to different types of gangliosides. Both hPIV-1 and
hPIV-3 preferentially bound to neolacto-series gangliosides containing
a terminal N-acetylneuraminic acid (NeuAc) linked to
N-acetyllactosamine (Gal
1-4GlcNAc) by the
2-3
linkage (NeuAc
2-3Gal
1-4GlcNAc). Unlike hPIV-1, hPIV-3 bound to
gangliosides with a terminal NeuAc linked to Gal
1-4GlcNAc through an
2-6 linkage (NeuAc
2-6Gal
1-4GlcNAc) or to gangliosides with a
different sialic acid, N-glycolylneuraminic acid
(NeuGc), linked to Gal
1-4GlcNAc (NeuGc
2-3Gal
1-4GlcNAc). These
results indicate that the molecular species of glycoconjugate that
hPIV-1 recognizes are more limited than those recognized by hPIV-3.
Further analysis using purified gangliosides revealed that the
oligosaccharide core structure is also an important element for
binding. Gangliosides that contain branched
N-acetyllactosaminoglycans in their core structure
showed higher avidity than those without them. Agglutination of human, cow, and guinea pig erythrocytes but not equine erythrocytes by hPIV-1
and hPIV-3 correlated well with the presence or the absence of sialic
acid-linked branched N-acetyllactosaminoglycans on the cell surface. Finally, NeuAc
2-3I, which bound to both viruses, inhibited virus infection of Lewis lung carcinoma-monkey kidney cells
in a dose-dependent manner. We conclude that hPIV-1 and hPIV-3
preferentially recognize oligosaccharides containing branched N-acetyllactosaminoglycans with terminal NeuAc
2-3Gal
as receptors and that hPIV-3 also recognizes NeuAc
2-6Gal- or
NeuGc
2-3Gal-containing receptors. These findings provide important
information that can be used to develop inhibitors that prevent human
parainfluenza virus infection.
This article has been cited by other articles:
| J. Bacteriol. | Mol. Cell. Biol. | Microbiol. Mol. Biol. Rev. |
|---|
| Clin. Vaccine Immunol. | ALL ASM JOURNALS |
|---|