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Journal of Virology, December 2000, p. 11825-11831, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Sialic Acid Species as a Determinant of the Host Range of Influenza A Viruses

Yasuo Suzuki,1 Toshihiro Ito,2 Takashi Suzuki,1 Robert E. Holland Jr.,3 Thomas M. Chambers,3 Makoto Kiso,4 Hideharu Ishida,4 and Yoshihiro Kawaoka5,6,*

Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Yada, Shizuoka-shi 422-8526,1 Department of Veterinary Public Health, Faculty of Agriculture, Tottori University, Tottori 680-8553,2 Department of Applied Bioorganic Chemistry, Gifu University, Gifu 501-1193,4 and Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639,6 Japan; Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 405463; and Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 537065

Received 3 May 2000/Accepted 14 September 2000

The distribution of sialic acid (SA) species varies among animal species, but the biological role of this variation is largely unknown. Influenza viruses differ in their ability to recognize SA-galactose (Gal) linkages, depending on the animal hosts from which they are isolated. For example, human viruses preferentially recognize SA linked to Gal by the alpha 2,6(SAalpha 2,6Gal) linkage, while equine viruses favor SAalpha 2,3Gal. However, whether a difference in relative abundance of specific SA species (N-acetylneuraminic acid [NeuAc] and N-glycolylneuraminic acid [NeuGc]) among different animals affects the replicative potential of influenza viruses is uncertain. We therefore examined the requirement for the hemagglutinin (HA) for support of viral replication in horses, using viruses whose HAs differ in receptor specificity. A virus with an HA recognizing NeuAcalpha 2,6Gal but not NeuAcalpha 2,3Gal or NeuGcalpha 2,3Gal failed to replicate in horses, while one with an HA recognizing the NeuGcalpha 2,3Gal moiety replicated in horses. Furthermore, biochemical and immunohistochemical analyses and a lectin-binding assay demonstrated the abundance of the NeuGcalpha 2,3Gal moiety in epithelial cells of horse trachea, indicating that recognition of this moiety is critical for viral replication in horses. Thus, these results provide evidence of a biological effect of different SA species in different animals.


* 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.


Journal of Virology, December 2000, p. 11825-11831, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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