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Journal of Virology, October 2000, p. 9300-9305, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Recognition of N-Glycolylneuraminic Acid Linked to Galactose by the alpha 2,3 Linkage Is Associated with Intestinal Replication of Influenza A Virus in Ducks

Toshihiro Ito,1 Yasuo Suzuki,2 Takashi Suzuki,2 Ayato Takada,3 Taisuke Horimoto,4 Krisna Wells,5 Hiroshi Kida,3 Koichi Otsuki,1 Makoto Kiso,6 Hideharu Ishida,6 and Yoshihiro Kawaoka5,7,*

Department of Veterinary Public Health, Faculty of Agriculture, Tottori University, Tottori 680-8553,1 Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Science, Shizuoka 422-8002,2 Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818,3 Department of Veterinary Microbiology, College of Agriculture, Osaka Prefecture University, Sakai 599-6231,4 Department of Applied Bioorganic Chemistry, Gifu University, Gifu 501-1193,6 and Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639,7 and Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin---Madison, Madison, Wisconsin 537065

Received 17 December 1999/Accepted 16 May 2000

The hemagglutinin (HA) of H3 human influenza viruses does not support viral replication in duck intestine despite its avian origin. A Leu-to-Gln mutation at position 226 and a Ser-to-Gly mutation at position 228 in the HA of human A/Udorn/307/72 (H3N2) permit a reassortant virus [human Udorn HA, with all other genes from A/mallard/New York/6750/78 (H2N2)] to replicate in ducks. To understand the molecular basis of this change in host range restriction, we investigated the receptor specificity of duck influenza viruses as well as of human-duck virus reassortants. The results indicate that the recognition of a glycoconjugate moiety possessing N-glycolneuramic acid (NeuGc) linked to galactose by the alpha 2,3 linkage (NeuGcalpha 2,3Gal) is associated with viral replication in duck intestine. Immunofluorescence assays with NeuGcalpha 2,3Gal-specific antiserum detected this moiety primarily on the crypt epithelial cells of duck colon. Such recognition, together with biochemical evidence of NeuGc in crypt cells, correlated exactly with the ability of the virus to replicate in duck colon. These results suggest that recognition of the NeuGcalpha 2,3-Gal moiety plays an important role in the enterotropism of avian influenza viruses.


* 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, October 2000, p. 9300-9305, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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