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Journal of Virology, September 1998, p. 7626-7631, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Role of Influenza A Virus Hemagglutinin Residues 226 and 228 in Receptor Specificity and Host Range Restriction

Angela Vines,1,dagger Krisna Wells,1,2 Mikhail Matrosovich,1 Maria R. Castrucci,3 Toshihiro Ito,4 and Yoshihiro Kawaoka1,2,5,*

Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 381051; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin---Madison, Madison, Wisconsin 537062; Department of Virology, Instituto Superiore di Sanita, 00161 Rome, Italy3; Department of Veterinary Public Health, Faculty of Agriculture, Tottori University, Tottori 680, Japan4; and Department of Pathology, University of Tennessee, Memphis, Memphis, Tennessee 381635

Received 13 March 1998/Accepted 19 May 1998

Influenza A viruses can be isolated from a variety of animals, but their range of hosts is restricted. For example, human influenza viruses do not replicate in duck intestine, the major replication site of avian viruses in ducks. Although amino acids at positions 226 and 228 of hemagglutinin (HA) of the H3 subtype are known to be important for this host range restriction, the contributions of specific amino acids at these positions to restriction were not known. Here, we address this issue by generating HAs with site-specific mutations of a human virus that contain different amino acid residues at these positions. We also let ducks select replication-competent viruses from a replication-incompetent virus containing a human virus HA by inoculating animals with 1010.5 50% egg infectious dose of the latter virus and identified a mutation in the HA. Our results showed that the Ser-to-Gly mutation at position 228, in addition to the Leu-to-Gln mutation at position 226 of the HA of the H3 subtype, is critical for human virus HA to support virus replication in duck intestine.

* 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.

dagger Present address: Department of Biology, Spelman College, Atlanta, GA 30314-4399.

Journal of Virology, September 1998, p. 7626-7631, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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